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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment
Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim
Cancer Res Treat. 2020;52(1):98-108.   Published online May 27, 2019
DOI: https://doi.org/10.4143/crt.2019.195
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

Citations

Citations to this article as recorded by  
  • Exploring Multiplex Immunohistochemistry (mIHC) Techniques and Histopathology Image Analysis: Current Practice and Potential for Clinical Incorporation
    Aria Kaiyuan Sun, Song Fan, Siu Wai Choi
    Cancer Medicine.2025;[Epub]     CrossRef
  • The immunologic phenotype of thrombi is associated with future vascular events after cerebral infarction
    Wookjin Yang, Soon Auck Hong, Jeong-Min Kim, Hae-Bong Jeong, Taek-Kyun Nam, Hyun Ho Choi, Suh Min Kim, Kwang-Yeol Park, Hye Ryoun Kim
    Journal of NeuroInterventional Surgery.2024; 16(4): 352.     CrossRef
  • The tumor immune microenvironment remodeling and response to HER2‐targeted therapy in HER2‐positive advanced gastric cancer
    Lei Jiang, Xingwang Zhao, Yilin Li, Yajie Hu, Yu Sun, Shengde Liu, Zizhen Zhang, Yanyan Li, Xujiao Feng, Jiajia Yuan, Jian Li, Xiaotian Zhang, Yang Chen, Lin Shen
    IUBMB Life.2024; 76(7): 420.     CrossRef
  • HCR spectral imaging: 10-plex, quantitative, high-resolution RNA and protein imaging in highly autofluorescent samples
    Samuel J. Schulte, Mark E. Fornace, John K. Hall, Grace J. Shin, Niles A. Pierce
    Development.2024;[Epub]     CrossRef
  • iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice
    Jihye Kim, Jee Hyun Kim, Younghoon Kim, Jooyoung Lee, Hyun Jung Lee, Seong-Joon Koh, Jong Pil Im, Joo Sung Kim
    Histochemistry and Cell Biology.2024; 162(5): 415.     CrossRef
  • Immunohistochemistry for assessing toxicity and mechanism of action of anticancer drugs during preclinical trials. From theory to practice
    M. A. Dodokhova, M. A. Akimenko, O. V. Voronova, M. S. Alkhusein-Kulyaginova, N. A. Kornienko, M. V. Gulyan, D. N. Gyulmamedov, M.-M. Kh. Alasheva, E. Sh. Kazimagomedova, D. B. Shpakovsky, E. R. Milaeva, I. M. Kotieva
    Fundamental and Clinical Medicine.2024; 9(3): 74.     CrossRef
  • Nontoxic Fluorescent Nanoprobes for Multiplexed Detection and 3D Imaging of Tumor Markers in Breast Cancer
    Pavel Sokolov, Galina Nifontova, Pavel Samokhvalov, Alexander Karaulov, Alyona Sukhanova, Igor Nabiev
    Pharmaceutics.2023; 15(3): 946.     CrossRef
  • Automatic generation of pathological benchmark dataset from hyperspectral images of double stained tissues
    Jiansheng Wang, Xintian Mao, Yan Wang, Xiang Tao, Junhao Chu, Qingli Li
    Optics & Laser Technology.2023; 163: 109331.     CrossRef
  • Heterogeneity of the Tumor Microenvironment Across Molecular Subtypes of Breast Cancer
    Dharambir Kashyap, Amanjit Bal, Santosh Irinike, Siddhant Khare, Shalmoli Bhattacharya, Ashim Das, Gurpreet Singh
    Applied Immunohistochemistry & Molecular Morphology.2023; 31(8): 533.     CrossRef
  • Exploring the Complex and Multifaceted Interplay between Melanoma Cells and the Tumor Microenvironment
    Magdalena Kuras
    International Journal of Molecular Sciences.2023; 24(18): 14403.     CrossRef
  • New insights into the tumour immune microenvironment of nasopharyngeal carcinoma
    Aisling Forder, Greg L. Stewart, Nikita Telkar, Wan L. Lam, Cathie Garnis
    Current Research in Immunology.2022; 3: 222.     CrossRef
  • Let us not forget about our past contributions to the field of prostatic neoplasms: To some extent what we value now was already there
    Rodolfo Montironi, Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Gregor Mikuz
    Pathology - Research and Practice.2021; 219: 153377.     CrossRef
  • Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate -Induced Gastritis
    Du-Min Go, Seung Hyun Lee, Su-Hyung Lee, Sang-Ho Woo, Kibyeong Kim, Kyeongdae Kim, Kyu Seong Park, Jong-Hwan Park, Sang-Jun Ha, Woo Ho Kim, Jae-Hoon Choi, Dae-Yong Kim
    Cellular and Molecular Gastroenterology and Hepatology.2021; 12(2): 715.     CrossRef
  • Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry
    Yujun Park, An Na Seo, Jiwon Koh, Soo Kyoung Nam, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
    OncoImmunology.2021;[Epub]     CrossRef
  • Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry
    Hee Young Na, Yujun Park, Soo Kyung Nam, Jiwon Koh, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Kyu Sang Lee, Hye Seung Lee
    Journal of Translational Medicine.2021;[Epub]     CrossRef
  • Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers
    Rui Wei, Si Liu, Shutian Zhang, Li Min, Shengtao Zhu
    Analytical Cellular Pathology.2020; 2020: 1.     CrossRef
  • Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy
    Laura Bracci, Alessandra Fragale, Lucia Gabriele, Federica Moschella
    Frontiers in Immunology.2020;[Epub]     CrossRef
  • 9,783 View
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Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF
Jae-Hyeon Kim, Jun-Ho Ahn, Michael Lee
Cancer Res Treat. 2017;49(4):947-959.   Published online January 3, 2017
DOI: https://doi.org/10.4143/crt.2016.280
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Intrinsic and acquired resistance limit the therapeutic benefits of inhibitors of oncogenic BRAF in melanoma. To identify microRNAs (miRNAs) associated with resistance to a BRAF inhibitor, we compared miRNA expression levels in three cell lines with different BRAF inhibitor sensitivity.
Materials and Methods
miRNA microarray analysis was conducted to compare miRNA expression levels. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to confirm the expression of differentially expressed miRNAs. The cellular effects of miR-1246 were further examined by MTT assay, immunoblotting analysis, cell cycle analysis, flow cytometric assay of apoptosis, and autophagy assay.
Results
The miRNA microarray analysis and qRT-PCR identified five miRNAs (miR-3617, miR-92a-1, miR-1246, miR-193b-3p, and miR-17-3p) with expression that was consistently altered in two BRAF inhibitor-resistant cell lines. Among the five miRNAs, a miR-1246 mimic significantly reduced the antiproliferative effects of the BRAF inhibitor PLX4720 in BRAF inhibitor–resistant A375P (A375P/Mdr) cells, suggesting that miR-1246 upregulation confers acquired resistance to BRAF inhibition. In particular, apoptosis was identified as a major type of cell death in miR-1246–transfected cells; however, necrosis predominated in mimic-control-transfected cells, indicating that the resistance to PLX4720 in miR-1246 mimic-transfected cells is predominantly due to a reduction in necrosis. Furthermore, we found that miR-1246 promoted G2/M arrest through autophagy as a way to escape cell death by necrosis and apoptosis in response to PLX4720. The promotion of BRAF inhibitor resistance by miR-1246 was associated with lowered levels of p-ERK.
Conclusion
These results suggest that miR-1246 may be a potential therapeutic target in melanoma with acquired resistance to BRAF inhibitors.

Citations

Citations to this article as recorded by  
  • Non-coding RNAs in BRAF-mutant melanoma: targets, indicators, and therapeutic potential
    S. Afsar, Rahamat Unissa Syed, Weam M. A. Khojali, Najat Masood, Mhdia Elhadi Osman, J. Siva Jyothi, Mohd. Abdul Hadi, Amna Abakar Suleiman Khalifa, Nayla Ahmed Mohammed Aboshouk, Hessa Ahmed Alsaikhan, Aljuri Saleh Alafnan, Bushra Abdullah Alrashidi
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(1): 297.     CrossRef
  • Tumor microenvironment responded naturally extracted FOF1-ATPase loaded chromatophores for antitumor therapy
    Weiyong Hong, Bang Lou, Ying Gao, Hui Zhao, Sanjun Ying, Saicheng Yang, Hanbing Li, Qingliang Yang, Gensheng Yang
    International Journal of Biological Macromolecules.2023; 230: 123127.     CrossRef
  • MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation
    Elizabeth Proaño-Pérez, Laia Ollé, Yanru Guo, Cristina Aparicio, Mario Guerrero, Rosa Muñoz-Cano, Margarita Martin
    International Journal of Molecular Sciences.2023; 24(4): 3515.     CrossRef
  • Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective
    Elisabetta Fratta, Giorgio Giurato, Roberto Guerrieri, Francesca Colizzi, Jessica Dal Col, Alessandro Weisz, Agostino Steffan, Barbara Montico
    Cell Death Discovery.2023;[Epub]     CrossRef
  • BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers
    Giorgia Castellani, Mariachiara Buccarelli, Maria Beatrice Arasi, Stefania Rossi, Maria Elena Pisanu, Maria Bellenghi, Carla Lintas, Claudio Tabolacci
    Cancers.2023; 15(16): 4026.     CrossRef
  • METTL3 promotes Non-Small-Cell Lung Cancer Growth and Metastasis by Inhibiting FDX1 Through Copper Death-Associated Pri-miR-21-5p Maturation
    Shuai Qian, Jun Liu, Wenliang Liao, Fengping Wang
    Epigenomics.2023; 15(23): 1237.     CrossRef
  • A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers
    Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Mohammad Taheri, Mohammad Samadian
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
  • Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
    Lauretta Levati, Cristian Bassi, Simona Mastroeni, Laura Lupini, Gian Carlo Antonini Cappellini, Laura Bonmassar, Ester Alvino, Simona Caporali, Pedro Miguel Lacal, Maria Grazia Narducci, Ivan Molineris, Federica De Galitiis, Massimo Negrini, Giandomenico
    Cancers.2022; 14(15): 3706.     CrossRef
  • Paradoxical downregulation of LPAR3 exerts tumor-promoting activity through autophagy induction in Ras-transformed cells
    Sung-Hee Hwang, Hye-Gyo Kim, Michael Lee
    BMC Cancer.2022;[Epub]     CrossRef
  • SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors
    Elizabeth Proaño-Pérez, Eva Serrano-Candelas, Cindy Mancia, Arnau Navinés-Ferrer, Mario Guerrero, Margarita Martin
    Cancers.2022; 14(24): 6198.     CrossRef
  • Carfilzomib in Combination with Bortezomib Enhances Apoptotic Cell Death in B16-F1 Melanoma Cells
    Min Seung Lee, So Hyun Lim, Ah-Ran Yu, Chi Yeon Hwang, Insug Kang, Eui-Ju Yeo
    Biology.2021; 10(2): 153.     CrossRef
  • Resistance to Molecularly Targeted Therapies in Melanoma
    Meet Patel, Adam Eckburg, Shahina Gantiwala, Zachary Hart, Joshua Dein, Katie Lam, Neelu Puri
    Cancers.2021; 13(5): 1115.     CrossRef
  • Learning from Embryogenesis—A Comparative Expression Analysis in Melanoblast Differentiation and Tumorigenesis Reveals miRNAs Driving Melanoma Development
    Lisa Linck-Paulus, Lisa Lämmerhirt, Daniel Völler, Katharina Meyer, Julia C. Engelmann, Rainer Spang, Norbert Eichner, Gunter Meister, Silke Kuphal, Anja Katrin Bosserhoff
    Journal of Clinical Medicine.2021; 10(11): 2259.     CrossRef
  • METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246
    Xuehan Bi, Xiao Lv, Dajiang Liu, Hongtao Guo, Guang Yao, Lijuan Wang, Xiaolei Liang, Yongxiu Yang
    Cell Death Discovery.2021;[Epub]     CrossRef
  • Choosing The Right Animal Model for Renal Cancer Research
    Paweł Sobczuk, Anna Brodziak, Mohammed Imran Khan, Stuti Chhabra, Michał Fiedorowicz, Marlena Wełniak-Kamińska, Kamil Synoradzki, Ewa Bartnik, Agnieszka Cudnoch-Jędrzejewska, Anna M. Czarnecka
    Translational Oncology.2020; 13(3): 100745.     CrossRef
  • Circulating microRNAs as biomarkers for early diagnosis of cutaneous melanoma
    Sara Carpi, Beatrice Polini, Stefano Fogli, Adriano Podestà, Erkko Ylösmäki, Vincenzo Cerullo, Antonella Romanini, Paola Nieri
    Expert Review of Molecular Diagnostics.2020; 20(1): 19.     CrossRef
  • Autophagy inhibition in 3T3-L1 adipocytes breaks the crosstalk with tumor cells by suppression of adipokine production
    Sung-Hee Hwang, Michael Lee
    Animal Cells and Systems.2020; 24(1): 17.     CrossRef
  • Roles of S100 family members in drug resistance in tumors: Status and prospects
    Xin Hua, Hongming Zhang, Jinfang Jia, Shanshan Chen, Yue Sun, Xiaoli Zhu
    Biomedicine & Pharmacotherapy.2020; 127: 110156.     CrossRef
  • MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors
    Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio, Paolo Antonio Ascierto, Maria Vincenza Carriero
    International Journal of Molecular Sciences.2020; 21(12): 4544.     CrossRef
  • Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains
    Loredana Guglielmi, Marta Nardella, Carla Musa, Ingrid Cifola, Manuela Porru, Beatrice Cardinali, Ilaria Iannetti, Chiara Di Pietro, Giulia Bolasco, Valentina Palmieri, Laura Vilardo, Nicolò Panini, Fabrizio Bonaventura, Massimiliano Papi, Ferdinando Scav
    Cancers.2020; 12(6): 1635.     CrossRef
  • MiR‐1246 promotes anti‐apoptotic effect of mini‐αA in oxidative stress‐induced apoptosis in retinal pigment epithelial cells
    Qianyin Chen, Huimin Lin, Xuan Deng, Shengnan Li, Jinglin Zhang
    Clinical & Experimental Ophthalmology.2020; 48(5): 682.     CrossRef
  • Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review
    Ilaria Proietti, Nevena Skroza, Nicoletta Bernardini, Ersilia Tolino, Veronica Balduzzi, Anna Marchesiello, Simone Michelini, Salvatore Volpe, Alessandra Mambrin, Giorgio Mangino, Giovanna Romeo, Patrizia Maddalena, Catherine Rees, Concetta Potenza
    Cancers.2020; 12(10): 2801.     CrossRef
  • The potential of BRAF-associated non-coding RNA as a therapeutic target in melanoma
    Luigi Fattore, Rita Mancini, Paolo Antonio Ascierto, Gennaro Ciliberto
    Expert Opinion on Therapeutic Targets.2019; 23(1): 53.     CrossRef
  • A plasma microRNA biomarker of melanoma as a personalised assessment of treatment response
    Ryan K. van Laar, Mitchel T. Lincoln, Barton J. van Laar
    Melanoma Research.2019; 29(1): 19.     CrossRef
  • A three plasma microRNA signature for papillary thyroid carcinoma diagnosis in Chinese patients
    Zhiyan Wang, Jinru Lv, Xuan Zou, Zebo Huang, Huo Zhang, Qingxie Liu, Lin Jiang, Xin Zhou, Wei Zhu
    Gene.2019; 693: 37.     CrossRef
  • The origin of exosomal miR-1246 in human cancer cells
    Yi-Fan Xu, Bethany N. Hannafon, Ujjwol Khatri, Amy Gin, Wei-Qun Ding
    RNA Biology.2019; 16(6): 770.     CrossRef
  • Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF Inhibitor Revealed by RNA-Seq Analysis
    Jun-Ho Ahn, Sung-Hee Hwang, Hyun-Soo Cho, Michael Lee
    Biomolecules & Therapeutics.2019; 27(3): 302.     CrossRef
  • MicroRNA heterogeneity in melanoma progression
    Anita Thyagarajan, Kenneth Y. Tsai, Ravi P. Sahu
    Seminars in Cancer Biology.2019; 59: 208.     CrossRef
  • miR-126-3p down-regulation contributes to dabrafenib acquired resistance in melanoma by up-regulating ADAM9 and VEGF-A
    Simona Caporali, Adriana Amaro, Lauretta Levati, Ester Alvino, Pedro Miguel Lacal, Simona Mastroeni, Federica Ruffini, Laura Bonmassar, Gian Carlo Antonini Cappellini, Nadia Felli, Alessandra Carè, Ulrich Pfeffer, Stefania D’Atri
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • MicroRNA-1246 regulates the radio-sensitizing effect of curcumin in bladder cancer cells via activating P53
    Ran Xu, Huabing Li, Shuiqing Wu, Jian Qu, Haiyan Yuan, Yangang Zhou, Qiong Lu
    International Urology and Nephrology.2019; 51(10): 1771.     CrossRef
  • The “-OMICS” facet of melanoma: Heterogeneity of genomic, proteomic and metabolomic biomarkers
    Douglas Donnelly, Phyu P. Aung, George Jour
    Seminars in Cancer Biology.2019; 59: 165.     CrossRef
  • Upregulation of S100A9 contributes to the acquired resistance to BRAF inhibitors
    Sung-Hee Hwang, Jun-Ho Ahn, Michael Lee
    Genes & Genomics.2019; 41(11): 1273.     CrossRef
  • Targeting CDC7 sensitizes resistance melanoma cells to BRAFV600E-specific inhibitor by blocking the CDC7/MCM2-7 pathway
    Shaimaa A. Gad, Hamdy E. A. Ali, Rofaida Gaballa, Rania M. Abdelsalam, Mourad Zerfaoui, Hamed I. Ali, Salwa H. Salama, Sanaa A. Kenawy, Emad Kandil, Zakaria Y. Abd Elmageed
    Scientific Reports.2019;[Epub]     CrossRef
  • The Role of Autophagy in the Resistance to BRAF Inhibition in BRAF-Mutated Melanoma
    Xiao Liu, Jinfeng Wu, Haihong Qin, Jinhua Xu
    Targeted Oncology.2018; 13(4): 437.     CrossRef
  • Targeting signal-transducer-and-activator-of-transcription 3 sensitizes human cutaneous melanoma cells to BRAF inhibitor
    Xiaohui Wang, Huajun Qu, Yinghe Dong, Guozhi Wang, Yuchen Zhen, Linxia Zhang
    Cancer Biomarkers.2018; 23(1): 67.     CrossRef
  • Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4
    Li-Jun Mo, Man Song, Qiao-Hua Huang, Hua Guan, Xiao-Dan Liu, Da-Fei Xie, Bo Huang, Rui-Xue Huang, Ping-Kun Zhou
    British Journal of Cancer.2018; 119(4): 492.     CrossRef
  • An oasis in the desert of cancer chemotherapeutic resistance: The enlightenment from reciprocal crosstalk between signaling pathways of UPR and autophagy in cancers
    Yuhang Zhang, Xianjun Qu, Lingfan Jiang
    Biomedicine & Pharmacotherapy.2017; 92: 972.     CrossRef
  • 12,547 View
  • 397 Download
  • 37 Web of Science
  • 37 Crossref
Close layer
Maspin Suppresses Survival of Lung Cancer Cells through Modulation of Akt Pathway
Eunsook Nam, Chaehwa Park
Cancer Res Treat. 2010;42(1):42-47.   Published online March 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.1.42
AbstractAbstract PDFPubReaderePub
Purpose

Maspin is a tumor suppressor protein that has been reported to stimulate the cell death of cancer and inhibit the metastasis of cancer. The present study aimed to explore the survival pathway by which maspin modulates the resistance of human lung cancer cells to chemotherapeutic drugs, and the consequences of maspin gene therapy in an animal model.

Materials and Methods

NCI-H157 and A549 cells were transfected with either a mock vector (pCMVTaq4C), maspin (pCMV-maspin), siControl or siMaspin. RT-PCR and Western blot analysis were performed to study the expressions of survival proteins in lung cancer. cDNA microarray analysis was carried out to compare the maspin-modulated gene expression between the xenograft tumors derived from the lung cancer cells that were stably transfected with pCMVTaq4C or pCMV-maspin. Maspin gene therapy was performed by intra-tumoral injections of pCMVTaq4C or pCMV-maspin into the pre-established subcutaneous tumors in nude mice.

Results

Maspin significantly decreased the survival to doxorubicin and etoposide, whereas did not affect the survival to cisplatin in the NCI-H157 cells. Interestingly, transfection with a maspin plasmid resulted in a significant reduction of the phosphorylation of Akt in the NCI-H157 cells, whereas knockdown of maspin increased the phosphorylation of Akt in the A549 cells. Microarray analysis of the xenograft tumors revealed a specific gene expression profile, demonstrating that maspin is associated with the differential expressions of PTEN and IGF2R. Direct transfer of pCMV-maspin into the tumor significantly retarded the tumor growth in the animal experiments (p=0.0048).

Conclusion

Lung cancer cells lacking maspin could be resistant to chemotherapeutic drugs such as doxorubicin or etoposide, at least in part by maintaining Akt phosphorylation.

Citations

Citations to this article as recorded by  
  • AKBA inhibits radiotherapy resistance in lung cancer by inhibiting maspin methylation and regulating the AKT/FOXO1/p21 axis
    Chun Gong, Wei Li, Jing Wu, Yao-Yao Li, Yi Ma, Li-Wen Tang
    Journal of Radiation Research.2023; 64(1): 33.     CrossRef
  • Investigation of the Subcellular Localization-Dependent Anti- or Pro-Tumor Functions of Maspin in Human Lung Adenocarcinoma Cell Line
    Takahiro Matsushige, Tomohiko Sakabe, Yoshihisa Umekita
    Yonago Acta Medica.2022; 65(1): 44.     CrossRef
  • Proteome and secretome analysis of pancreatic cancer cells
    Xiang Li, Hui Liu, Matthew D. Dun, Sam Faulkner, Xiaoming Liu, Chen Chen Jiang, Hubert Hondermarck
    PROTEOMICS.2022;[Epub]     CrossRef
  • AF8c, a Multi-Kinase Inhibitor Induces Apoptosis by Activating DR5/Nrf2 via ROS in Colorectal Cancer Cells
    Soyeon Jeong, Ahmed K. Farag, Hye Kyeong Yun, Yoon A. Jeong, Dae Yeong Kim, Min Jee Jo, Seong Hye Park, Bo Ram Kim, Jung Lim Kim, Bu Gyeom Kim, Dae-Hee Lee, Eun Joo Roh, Sang Cheul Oh
    Cancers.2022; 14(13): 3043.     CrossRef
  • Role of cytoplasmic localization of maspin in promoting cell invasion in breast cancer with aggressive phenotype
    Tomohiko Sakabe, Makoto Wakahara, Goshi Shiota, Yoshihisa Umekita
    Scientific Reports.2021;[Epub]     CrossRef
  • The potential function of IKKα in gastric precancerous lesion via mediating Maspin
    Ning Wang, Li-Li Chang
    Tissue and Cell.2020; 65: 101349.     CrossRef
  • The roles of MASPIN expression and subcellular localization in non-small cell lung cancer
    Xiao-Fei Wang, Bo Liang, Da-Xiong Zeng, Wei Lei, Cheng Chen, Yan-Bin Chen, Jian-An Huang, Ning Gu, Ye-Han Zhu
    Bioscience Reports.2020;[Epub]     CrossRef
  • The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma
    Klara Fodor, Nikoletta Dobos, Andrew Schally, Zita Steiber, Gabor Olah, Eva Sipos, Lorant Szekvolgyi, Gabor Halmos
    Oncotarget.2020; 11(2): 175.     CrossRef
  • Inhibition of miR-21-5p suppresses high glucose-induced proliferation and angiogenesis of human retinal microvascular endothelial cells by the regulation of AKT and ERK pathways via maspin
    Feng Qiu, Huijuan Tong, Yawen Wang, Jun Tao, Hailin Wang, Lei Chen
    Bioscience, Biotechnology, and Biochemistry.2018; 82(8): 1366.     CrossRef
  • Downregulating CD26/DPPIV by apigenin modulates the interplay between Akt and Snail/Slug signaling to restrain metastasis of lung cancer with multiple EGFR statuses
    Jer-Hwa Chang, Chao-Wen Cheng, Yi-Chieh Yang, Wan-Shen Chen, Wen-Yueh Hung, Jyh-Ming Chow, Pai-Sheng Chen, Michael Hsiao, Wei-Jiunn Lee, Ming-Hsien Chien
    Journal of Experimental & Clinical Cancer Research.2018;[Epub]     CrossRef
  • IKKα inibition by a glucosamine derivative enhances Maspin expression in osteosarcoma cell line
    Martina Leopizzi, Rossana Cocchiola, Edoardo Milanetti, Domenico Raimondo, Laura Politi, Cesare Giordano, Roberto Scandurra, Anna Scotto d'Abusco
    Chemico-Biological Interactions.2017; 262: 19.     CrossRef
  • Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways
    Jer-Hwa Chang, Shu-Leung Lai, Wan-Shen Chen, Wen-Yueh Hung, Jyh-Ming Chow, Michael Hsiao, Wei-Jiunn Lee, Ming-Hsien Chien
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2017; 1864(10): 1746.     CrossRef
  • Snail promotes cell migration through PI3K/AKT-dependent Rac1 activation as well as PI3K/AKT-independent pathways during prostate cancer progression
    Veronica Henderson, Basil Smith, Liza J Burton, Diandra Randle, Marisha Morris, Valerie A Odero-Marah
    Cell Adhesion & Migration.2015; 9(4): 255.     CrossRef
  • Docosahexaenoic Acid Induces Cell Death in Human Non-Small Cell Lung Cancer Cells by Repressing mTOR via AMPK Activation and PI3K/Akt Inhibition
    Nayeong Kim, Soyeon Jeong, Kaipeng Jing, Soyeon Shin, Soyeon Kim, Jun-Young Heo, Gi-Ryang Kweon, Seung-Kiel Park, Tong Wu, Jong-Il Park, Kyu Lim
    BioMed Research International.2015; 2015: 1.     CrossRef
  • Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines
    JUN ZHOU, QIN HUALONG, PENG ZHOU, FENG GUO
    International Journal of Molecular Medicine.2015; 36(5): 1440.     CrossRef
  • Cell-specific expression of artificial microRNAs targeting essential genes exhibit potent antitumor effect on hepatocellular carcinoma cells
    Chenyu Mao, Hao Liu, Ping Chen, Jingjia Ye, Lisong Teng, Zhenyu Jia, Jiang Cao
    Oncotarget.2015; 6(8): 5707.     CrossRef
  • TUBB3/βIII-Tubulin Acts through the PTEN/AKT Signaling Axis to Promote Tumorigenesis and Anoikis Resistance in Non–Small Cell Lung Cancer
    Joshua A. McCarroll, Pei Pei Gan, Rafael B. Erlich, Marjorie Liu, Tanya Dwarte, Sharon S. Sagnella, Mia C. Akerfeldt, Lu Yang, Amelia L. Parker, Melissa H. Chang, Michael S. Shum, Frances L. Byrne, Maria Kavallaris
    Cancer Research.2015; 75(2): 415.     CrossRef
  • Cancer Cell Resistance to Aurora Kinase Inhibitors: Identification of Novel Targets for Cancer Therapy
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    Clinical and Translational Medicine.2013;[Epub]     CrossRef
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    Journal of Huazhong University of Science and Technology [Medical Sciences].2012; 32(3): 346.     CrossRef
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    Thomas M. Bodenstine, Richard E. B. Seftor, Zhila Khalkhali-Ellis, Elisabeth A. Seftor, Philip A. Pemberton, Mary J. C. Hendrix
    Cancer and Metastasis Reviews.2012; 31(3-4): 529.     CrossRef
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    Evidence-Based Complementary and Alternative Medicine.2012; 2012: 1.     CrossRef
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    Journal of Thoracic Oncology.2012; 7(1): 20.     CrossRef
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    Cancer Prevention Research.2012; 5(5): 788.     CrossRef
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    Kyoung-Sub Song, Kaipeng Jing, Jong-Seok Kim, Eun-Jin Yun, Soyeon Shin, Kang-Sik Seo, Ji-Hoon Park, Jun-Young Heo, Jing X. Kang, Kwang-Sun Suh, Tong Wu, Jong-Il Park, Gi-Ryang Kweon, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim
    Pancreatology.2011; 11(6): 574.     CrossRef
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    Kyoung-Sub Song, Ge Li, Jong-Seok Kim, Kaipeng Jing, Tae-Dong Kim, Jin-Pyo Kim, Seung-Bo Seo, Jae-Kuk Yoo, Hae-Duck Park, Byung-Doo Hwang, Kyu Lim, Wan-Hee Yoon
    BMC Cancer.2011;[Epub]     CrossRef
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    Kaipeng Jing, Kyoung-Sub Song, Soyeon Shin, Nayeong Kim, Soyeon Jeong, Hye-Rim Oh, Ji-Hoon Park, Kang-Sik Seo, Jun-Young Heo, Jeongsu Han, Jong-Il Park, Chang Han, Tong Wu, Gi-Ryang Kweon, Seung-Kiel Park, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim
    Autophagy.2011; 7(11): 1348.     CrossRef
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    PLoS ONE.2011; 6(9): e24595.     CrossRef
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Characterization of RhoA-mediated Chemoresistance in Gastric Cancer Cells
Won Ki Kang, Inkyoung Lee, Chaehwa Park
Cancer Res Treat. 2005;37(4):251-256.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.251
AbstractAbstract PDFPubReaderePub
Purpose

RhoA is a critical transducer of extracellular signals, which leads to organization of actin cytoskeleton, motility, adhesion and gene regulation. The present study aimed to explore whether RhoA influences the susceptibility of gastric cancer cells to chemotherapeutic drugs.

Materials and Methods

SNU638 cells were transfected with a mock vector (pcDNA3.1), RhoA (pcDNA/RhoA), or constitutively active RhoA (pcDNA/caRhoA). MTT assay and Western blot analysis were performed to study the growth response to several chemotherapeutic drugs in the gastric cancer cell line, SNU638, with different RhoA levels.

Results

RhoA significantly enhanced the resistance to lovastatin, 5-FU, taxol and vincristine, but did not affect the sensitivity to cisplatin or etoposide in SNU638. In the Western blot analysis, RhoA decreased the PARP cleavage, which was accompanied by a concurrent reductionin cell death. The gene expression profile after a cDNA microarray analysis demonstrated that RhoA was associated with the differential expression of 19 genes, including those involved in anti-oxidant defense, glucose metabolism, anti-apoptosis and protein turnover.

Conclusion

Gastric cancer cells with a high expression of RhoA could be resistant to chemotherapeutic drugs, such as taxol or vincristine, implying that treatment strategies aimed at inactivation of RhoA might be promising for improving the efficacy of these chemotherapeutic drugs.

Citations

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  • Mutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment
    Pengfei Yu, Can Hu, Guangyu Ding, Xiaoliang Shi, Jingli Xu, Yang Cao, Xiangliu Chen, Wei Wu, Qi Xu, Jingquan Fang, Xingmao Huang, Shaohua Yuan, Hui Chen, Zhizheng Wang, Ling Huang, Fei Pang, Yian Du, Xiangdong Cheng
    Nature Communications.2024;[Epub]     CrossRef
  • ARHGAP6 inhibits bladder cancer cell viability, migration, and invasion via β-catenin signaling and enhances mitomycin C sensitivity
    Weihua Chen, Mingyue Tan, Chao Yu, Guoqiang Liao, Dehui Kong, Jie Bai, Bo Yang, Hua Gong
    Human Cell.2023; 36(2): 786.     CrossRef
  • RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential
    Seungyoon Nam, Jung Ho Kim, Dae Ho Lee
    Frontiers in Genetics.2019;[Epub]     CrossRef
  • TFAP2E methylation promotes 5‑fluorourail resistance via exosomal miR‑106a‑5p and miR‑421 in gastric cancer MGC‑803 cells
    Sun Jingyue, Wang Xiao, Zha Juanmin, Li Wei, Li Daoming, Xu Hong
    Molecular Medicine Reports.2019;[Epub]     CrossRef
  • New therapeutic options opened by the molecular classification of gastric cancer
    Mihaela Chivu-Economescu, Lilia Matei, Laura G Necula, Denisa L Dragu, Coralia Bleotu, Carmen C Diaconu
    World Journal of Gastroenterology.2018; 24(18): 1942.     CrossRef
  • Effects of statins on the chemoresistance—The antagonistic drug-drug interactions versus the anti-cancer effects
    Yasin Ahmadi, Ramin Karimian, Yunes Panahi
    Biomedicine & Pharmacotherapy.2018; 108: 1856.     CrossRef
  • The role of cytoskeleton and adhesion proteins in the resistance to photodynamic therapy. Possible therapeutic interventions
    Gabriela Di Venosa, Christian Perotti, Alcira Batlle, Adriana Casas
    Photochemical & Photobiological Sciences.2015; 14(8): 1451.     CrossRef
  • G Protein–Coupled Receptor and RhoA-Stimulated Transcriptional Responses: Links to Inflammation, Differentiation, and Cell Proliferation
    Olivia M. Yu, Joan Heller Brown
    Molecular Pharmacology.2015; 88(1): 171.     CrossRef
  • Rho/ROCK signaling in motility and metastasis of gastric cancer
    Tasuku Matsuoka
    World Journal of Gastroenterology.2014; 20(38): 13756.     CrossRef
  • Temozolomide-modulated glioma proteome: Role of interleukin-1 receptor-associated kinase-4 (IRAK4) in chemosensitivity
    Durairaj M. Kumar, Vikas Patil, Bini Ramachandran, Murugesan V. Nila, Kuppamuthu Dharmalingam, Kumaravel Somasundaram
    PROTEOMICS.2013; 13(14): 2113.     CrossRef
  • Inhibition of melanoma development in the Nras(Q61K)::Ink4a−/− mouse model by the small molecule BI‐69A11
    Yongmei Feng, Eric Lau, Marzia Scortegagna, Chelsea Ruller, Surya K. De, Elisa Barile, Stan Krajewski, Pedro Aza‐Blanc, Roy Williams, Anthony B. Pinkerton, Michael Jackson, Lynda Chin, Maurizio Pellecchia, Marcus Bosenberg, Ze'ev A. Ronai
    Pigment Cell & Melanoma Research.2013; 26(1): 136.     CrossRef
  • Ovarian clear cell carcinomas: RHO GTPases may contribute to explain their singular biologic behavior
    Belen Canet, Cristina Pons, Iñigo Espinosa, Jaime Prat
    Human Pathology.2011; 42(6): 833.     CrossRef
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