Cancer Research and Treatment

Original Articles

The CXCR4 Antagonist AMD3100 Has Dual Effects on Survival and Proliferation of Myeloma Cells In Vitro: Ha-Yon Kim, Ji-Young Hwang, Seong-Woo Kim, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Deog-Yeon Jo; Cancer Res Treat. 2010;42(4):225-234. Published online December 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.4.225

Purpose

AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro.

Materials and Methods

The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay).

Results

AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions.

Conclusion

AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.

Citations

Citations to this article as recorded by

Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles
Eloi Parladé, Annabel García-Leon, Eric Voltà-Durán, Ugutz Unzueta, Ramon Mangues, Isolda Casanova, Antonio Villaverde, Esther Vázquez
European Journal of Pharmaceutics and Biopharmaceutics.2024; 202: 114410. CrossRef
Lyophilization of biomimetic amyloids preserves their regulatable, endocrine-like functions for nanoparticle release
Marianna TP Favaro, Hèctor López-Laguna, Eric Voltà-Durán, Lorena Alba-Castellon, Julieta M. Sánchez, Isolda Casanova, Ugutz Unzueta, Ramón Mangues, Antonio Villaverde, Esther Vázquez
Applied Materials Today.2024; 39: 102348. CrossRef
Time-Prolonged Release of Tumor-Targeted Protein–MMAE Nanoconjugates from Implantable Hybrid Materials
Naroa Serna, Aïda Falgàs, Annabel García-León, Ugutz Unzueta, Yáiza Núñez, Alejandro Sánchez-Chardi, Carlos Martínez-Torró, Ramón Mangues, Esther Vazquez, Isolda Casanova, Antonio Villaverde
Pharmaceutics.2022; 14(1): 192. CrossRef
Non-invasive detection and complementary diagnosis of liver metastases via chemokine receptor 4 imaging
Hua Yang, Shanshan Tan, Jingjuan Qiao, Yiting Xu, Zongxiang Gui, Yuguang Meng, Bin Dong, Guangda Peng, Oluwatosin Y. Ibhagui, Weiping Qian, Jimmy Lu, Zezhong Li, Guimin Wang, Jinping Lai, Lily Yang, Hans E. Grossniklaus, Jenny J. Yang
Cancer Gene Therapy.2022; 29(12): 1827. CrossRef
Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering
Eric Voltà-Durán, Olivia Cano-Garrido, Naroa Serna, Hèctor López-Laguna, Laura Sánchez-García, Mireia Pesarrodona, Alejandro Sánchez-Chardi, Ramón Mangues, Antonio Villaverde, Esther Vázquez, Ugutz Unzueta
Science China Materials.2020; 63(1): 147. CrossRef
Engineering Secretory Amyloids for Remote and Highly Selective Destruction of Metastatic Foci
María Virtudes Céspedes, Olivia Cano‐Garrido, Patricia Álamo, Rita Sala, Alberto Gallardo, Naroa Serna, Aïda Falgàs, Eric Voltà‐Durán, Isolda Casanova, Alejandro Sánchez‐Chardi, Hèctor López‐Laguna, Laura Sánchez‐García, Julieta M. Sánchez, Ugutz Unzueta,
Advanced Materials.2020;[Epub] CrossRef
Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles
Naroa Serna, Julieta M Sánchez, Ugutz Unzueta, Laura Sánchez-García, Alejandro Sánchez-Chardi, Ramón Mangues, Esther Vázquez, Antonio Villaverde
Nanotechnology.2019; 30(11): 115101. CrossRef
The Involvement of SDF-1α/CXCR4 Axis in Radiation-Induced Acute Injury and Fibrosis of Skin
Jinming Cao, Wei Zhu, Daojiang Yu, Lu Pan, Li Zhong, Yuji Xiao, Yiying Gao, Yang Jiao, Qi Zhang, Jiang Ji, Hongying Yang, Shuyu Zhang, Jianping Cao
Radiation Research.2019; 192(4): 410. CrossRef
Chemokine-mimetic plerixafor derivative for tumor-specific delivery of nanomaterials
Seungbeom Ko, Gayong Shim, Jinyoung Kim, Yu-Kyoung Oh
Nano Research.2018; 11(4): 2159. CrossRef
Protein Nanoparticles are nontoxic, Tuneable Cell Stressors
Marianna Teixeira de Pinho Favaro, Laura Sánchez-García, Alejandro Sánchez-Chardi, Mónica Roldán, Ugutz Unzueta, Naroa Serna, Olivia Cano-Garrido, Adriano Rodrigues Azzoni, Neus Ferrer-Miralles, Antonio Villaverde, Esther Vázquez
Nanomedicine.2018; 13(3): 255. CrossRef
Self-assembling toxin-based nanoparticles as self-delivered antitumoral drugs
Laura Sánchez-García, Naroa Serna, Patricia Álamo, Rita Sala, María Virtudes Céspedes, Mònica Roldan, Alejandro Sánchez-Chardi, Ugutz Unzueta, Isolda Casanova, Ramón Mangues, Esther Vázquez, Antonio Villaverde
Journal of Controlled Release.2018; 274: 81. CrossRef
The CXCR4 antagonist plerixafor (AMD3100) promotes proliferation of Ewing sarcoma cell lines in vitro and activates receptor tyrosine kinase signaling
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
Cell Communication and Signaling.2018;[Epub] CrossRef
Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Nanomedicine: Nanotechnology, Biology and Medicine.2018; 14(6): 1777. CrossRef
The inhibitory effects and mechanisms of 3,6-O-sulfated chitosan against human papillomavirus infection
Yanyun Gao, Wei Liu, Wei Wang, Xiaoshuang Zhang, Xia Zhao
Carbohydrate Polymers.2018; 198: 329. CrossRef
CXCL12/CXCR4/CXCR7 Chemokine Axis in the Central Nervous System: Therapeutic Targets for Remyelination in Demyelinating Diseases
Tianci Chu, Lisa B. E. Shields, Yi Ping Zhang, Shi-Qing Feng, Christopher B. Shields, Jun Cai
The Neuroscientist.2017; 23(6): 627. CrossRef
Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α–CXCR4 and TP53–TPM1 proteins
Chien‐Cheng Chen, Ching‐Wu Hsia, Cheng‐Wen Ho, Chang‐Min Liang, Chieh‐Min Chen, Kun‐Lun Huang, Bor‐Hwang Kang, Yi‐Hui Chen
Developmental Dynamics.2017; 246(3): 162. CrossRef
CXCL12 and CXCR7 are relevant targets to reverse cell adhesion‐mediated drug resistance in multiple myeloma
Johannes M. Waldschmidt, Anna Simon, Dagmar Wider, Stefan J. Müller, Marie Follo, Gabriele Ihorst, Sarah Decker, Joschka Lorenz, Manik Chatterjee, Abdel K. Azab, Justus Duyster, Ralph Wäsch, Monika Engelhardt
British Journal of Haematology.2017; 179(1): 36. CrossRef
CXCR4 blockade with AMD3100 enhances Taxol chemotherapy to limit ovarian cancer cell growth
Patrick M. Reeves, Mojgan A. Abbaslou, Farah R.W. Kools, Mark C. Poznansky
Anti-Cancer Drugs.2017; 28(9): 935. CrossRef
AMD3100: A Versatile Platform for CXCR4 Targeting 68Ga-Based Radiopharmaceuticals
Sophie Poty, Eleni Gourni, Pauline Désogère, Frédéric Boschetti, Christine Goze, Helmut R. Maecke, Franck Denat
Bioconjugate Chemistry.2016; 27(3): 752. CrossRef
The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines
Linn Reinholdt, Maria Bach Laursen, Alexander Schmitz, Julie Støve Bødker, Lasse Hjort Jakobsen, Martin Bøgsted, Hans Erik Johnsen, Karen Dybkær
Biomarker Research.2016;[Epub] CrossRef
PCAF-mediated Akt1 acetylation enhances the proliferation of human glioblastoma cells
Shuguang Zhang, Guan Sun, Zhimin Wang, Yi Wan, Jun Guo, Lei Shi
Tumor Biology.2015; 36(3): 1455. CrossRef
Chemokines and Bone
Annette Gilchrist, Paula H. Stern
Clinical Reviews in Bone and Mineral Metabolism.2015; 13(2): 61. CrossRef
AMD3100 reduces CXCR4-mediated survival and metastasis of osteosarcoma by inhibiting JNK and Akt, but not p38 or Erk1/2, pathways in in vitro and mouse experiments
YU-XIN LIAO, ZE-ZE FU, CHENG-HAO ZHOU, LIAN-CHENG SHAN, ZHUO-YING WANG, FEI YIN, LONG-PO ZHENG, YING-QI HUA, ZHENG-DONG CAI
Oncology Reports.2015; 34(1): 33. CrossRef
CXC Chemokine Ligand 12 Protects Pancreatic β-Cells from Necrosis through Akt Kinase-Mediated Modulation of Poly(ADP-ribose) Polymerase-1 Activity
Nevena Grdović, Svetlana Dinić, Mirjana Mihailović, Aleksandra Uskoković, Jelena Arambašić Jovanović, Goran Poznanović, Ludwig Wagner, Melita Vidaković, Malka Cohen-Armon
PLoS ONE.2014; 9(7): e101172. CrossRef
Potential therapeutic biomarkers in plasma cell myeloma: A flow cytometry study
Wenli Zheng, Dingshen Liu, Xiangshan Fan, Linda Powers, Maitrayee Goswami, Ying Hu, Pei Lin, L. Jeffrey Medeiros, Sa A. Wang
Cytometry Part B: Clinical Cytometry.2013; 84B(4): 222. CrossRef
Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology
Katharina Lückerath, Constantin Lapa, Annika Spahmann, Gerhard Jörg, Samuel Samnick, Andreas Rosenwald, Herrmann Einsele, Stefan Knop, Andreas K. Buck, Evren Alici
PLoS ONE.2013; 8(12): e84840. CrossRef
An Antedrug of the CXCL12 Neutraligand Blocks Experimental Allergic Asthma without Systemic Effect in Mice
François Daubeuf, Muriel Hachet-Haas, Patrick Gizzi, Vincent Gasparik, Dominique Bonnet, Valérie Utard, Marcel Hibert, Nelly Frossard, Jean-Luc Galzi
Journal of Biological Chemistry.2013; 288(17): 11865. CrossRef
EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells
WENJING FENG, XIZHEN XU, GANG ZHAO, GENG LI, TIANTIAN LIU, JUNJIE ZHAO, RUOLAN DONG, DAO WEN WANG, LING TU
International Journal of Molecular Medicine.2013; 32(3): 685. CrossRef
The role of the CXCL12-CXCR4/CXCR7 axis in the progression and metastasis of bone sarcomas (Review)
YU-XIN LIAO, CHENG-HAO ZHOU, HUI ZENG, DONG-QING ZUO, ZHUO-YING WANG, FEI YIN, YING-QING HUA, ZHENG-DONG CAI
International Journal of Molecular Medicine.2013; 32(6): 1239. CrossRef
Why and how to find neutraligands targeting chemokines?
Jean-Luc Galzi, Muriel Haas, Nelly Frossard, Marcel Hibert
Drug Discovery Today: Technologies.2012; 9(4): e245. CrossRef
Sublytic C5b‐9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy‐1 nephritis through TRAF6‐mediated PI3K‐dependent Akt1 activation
Wen Qiu, Yan Zhang, Xiaomei Liu, Jianbo Zhou, Yan Li, Ying Zhou, Kai Shan, Mei Xia, Nan Che, Xuefeng Feng, Dan Zhao, Yingwei Wang
The Journal of Pathology.2012; 226(4): 619. CrossRef
Initial Assessment of the Role of CXC Chemokine Receptor 4 after Polytrauma
Harold H. Bach, Vikas Saini, Todd A. Baker, Abhishek Tripathi, Richard L. Gamelli, Matthias Majetschak
Molecular Medicine.2012; 18(7): 1056. CrossRef
Differential effects of CXCR4 antagonists on the survival and proliferation of myeloid leukemia cellsin vitro
Ha-Yon Kim, Ji-Young Hwang, Yoon-Suk Oh, Seong-Woo Kim, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Young-Jun Yang, Deog-Yeon Jo
The Korean Journal of Hematology.2011; 46(4): 244. CrossRef

11,766 View
80 Download
33 Crossref

Cytoplasmic Trapping of CXCR4 in Hepatocellular Carcinoma Cell Lines: Seong-Woo Kim, Ha-Yon Kim, Ik-Chan Song, Seon-Ah Jin, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Deog-Yeon Jo; Cancer Res Treat. 2008;40(2):53-61. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.53

Abstract PDF PubReader ePub

Purpose

The chemokine receptor CXCR4 plays a role in the metastasis and progression of a broad range of malignant tumors; however, its influence on hepatocellular carcinoma (HCC) is not well defined. Thus, we analyzed the expression of CXCR4 and its functions in HCC cell lines in vitro.

Materials and Methods

Five HCC cell lines (HepG2, Hep3B, SK-HEP-1, NCI-H630 and PLC/PRF5) were investigated. The CXCR4 expression was analyzed by RT-PCR, Western blotting, flow cytometry and immunofluorescence staining. In addition, the effects of stromal cell-derived factor-1 (SDF-1) on the migration, proliferation and survival of the cells were investigated, as well as the SDF-1-induced phosphorylation of signaling molecules.

Results

All five cell lines had abundant CXCR4 in their cytoplasm, whereas a cell surface CXCR4 expression was only detected in a very small population of PLC/PRF5 cells. In contrast, SDF-1 bound to all the cells. SDF-1 induced the phosphorylation of AKT and ERK1/2 in the PLC/PRF5 cells and the phosphorylation of Stat3, AKT and ERK1/2 in the Hep3B cells. Nonetheless, SDF-1 did not induce migration or proliferation in any of the cells, nor did it rescue the cells from serum deprivation-induced apoptosis. Recruitment of CXCR4 from the cytoplasm to the cell surface was not elicited by dexamethasone, proinflammatory cytokines or VEGF. Hypoxia increased both the cytoplasmic and cell surface expressions of CXCR4 in only the PLC/PRF5 cells.

Conclusions

CXCR4 is trapped in the cytoplasm and it is not recruited to the cell surface by standard extrinsic stimuli in the majority of HCC cell lines, and the result of this is a negligible response to SDF-1.

Citations

Citations to this article as recorded by

CXCR4, regulated by HIF1A, promotes endometrial breakdown via CD45+ leukocyte recruitment in a mouse model of menstruation
Shufang Wang, Xihua Chen, Shige Guo, Fang Zhou, Xin Zhang, Cong Lu, Xuqing Yang, Qianxing Wang, Bin He, Jiedong Wang, Hanbi Wang, Xiangbo Xu
Reproductive Biology.2023; 23(3): 100785. CrossRef
Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
Megan M. Harper, Miranda Lin, Michael J. Cavnar, Prakash K. Pandalai, Reema A. Patel, Mei Gao, Joseph Kim, Ming Tan
PLOS ONE.2022; 17(7): e0270832. CrossRef
The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
Jan Korbecki, Klaudyna Kojder, Patrycja Kapczuk, Patrycja Kupnicka, Barbara Gawrońska-Szklarz, Izabela Gutowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
International Journal of Molecular Sciences.2021; 22(2): 843. CrossRef
Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
Daniel Kaemmerer, Robin Schindler, Franziska Mußbach, Uta Dahmen, Annelore Altendorf-Hofmann, Olaf Dirsch, Jörg Sänger, Stefan Schulz, Amelie Lupp
BMC Cancer.2017;[Epub] CrossRef
Role of C-X-C chemokine ligand 12/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma
Kuo-Shyang Jeng, Chi-Juei Jeng, Wen-Juei Jeng, Chiung-Fang Chang, I-Shyan Sheen
Oncology Letters.2017; 14(2): 1905. CrossRef
An Ultra‐High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4
Hua He, Xiaojuan Wang, Tiantian Cheng, Yongqing Xia, Jun Lao, Baosheng Ge, Hao Ren, Naseer Ullah Khan, Fang Huang
Chemistry – A European Journal.2016; 22(17): 5863. CrossRef
CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not
Maria Neve Polimeno, Caterina Ierano, Crescenzo D'Alterio, Nunzia Simona Losito, Maria Napolitano, Luigi Portella, Giosuè Scognamiglio, Fabiana Tatangelo, Anna Maria Trotta, Steven Curley, Susan Costantini, Raffaele Liuzzi, Francesco Izzo, Stefania Scala
Cellular & Molecular Immunology.2015; 12(4): 474. CrossRef
Mechanisms regulating cell membrane localization of the chemokine receptor CXCR4 in human hepatocarcinoma cells
Edgar B. Cepeda, Tatjana Dediulia, Joan Fernando, Esther Bertran, Gustavo Egea, Estanislao Navarro, Isabel Fabregat
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2015; 1853(5): 1205. CrossRef
Immunohistochemical Expression of CXCR4 on Breast Cancer and Its Clinical Significance
Marina Okuyama Kishima, Carlos Eduardo Coral de Oliveira, Bruna Karina Banin-Hirata, Roberta Losi-Guembarovski, Karen Brajão de Oliveira, Marla Karine Amarante, Maria Angelica Ehara Watanabe
Analytical Cellular Pathology.2015; 2015: 1. CrossRef
Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation
Sandra Pinto, Alicia Martínez-Romero, José-Enrique O’Connor, Rosario Gil-Benso, Teresa San-Miguel, Liria Terrádez, Carlos Monteagudo, Robert C Callaghan
BMC Cancer.2014;[Epub] CrossRef
Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal stem/stromal cells
Rebecca A Pelekanos, Michael J Ting, Varda S Sardesai, Jennifer M Ryan, Yaw-Chyn Lim, Jerry KY Chan, Nicholas M Fisk
BMC Cell Biology.2014;[Epub] CrossRef
Downregulation of the proangiogenic prostaglandin E receptor EP3 and reduced angiogenesis in a mouse model of diabetes mellitus
Kazuhito Oba, Kanako Hosono, Hideki Amano, Shin-ichiro Okizaki, Yoshiya Ito, Masayoshi Shichiri, Masataka Majima
Biomedicine & Pharmacotherapy.2014; 68(8): 1125. CrossRef
Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF-1α expression in vivo
HUAQI ZHU, QIMAN SUN, CHANGJUN TAN, MIN XU, ZHI DAI, ZHENG WANG, JIA FAN, JIAN ZHOU
Molecular Medicine Reports.2014; 10(2): 585. CrossRef
Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration
Caterina Ierano, Agnes Basseville, Kenneth K.W. To, Zhirong Zhan, Robert W. Robey, Julia Wilkerson, Susan E. Bates, Stefania Scala
Cancer Biology & Therapy.2013; 14(2): 175. CrossRef

11,222 View
60 Download
14 Crossref

First
Prev
Page of 1
Next
Last

Search