Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

作者: Benjamin D. Hedley , Jenny E. Chu , D. George Ormond , Michel S. Beausoleil , Alexandra Boasie

DOI: 10.1158/1078-0432.CCR-10-3298

关键词:

摘要: Purpose: Erythropoiesis-stimulating agents (ESAs) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced progression. However, minimal pre-clinical data is available regarding the impact of EPO on metastatic cell behavior and/or process, this was goal our study. Experimental Design: Breast lines were treated with recombinant human (rHuEPO) screened expression EPOR. MDA-MB-231 MDA-MB-435 functional assays vitro (2D/3D growth, survival) vivo (tumorigenicity, metastasis), presence or absence cytotoxic agents. Results: A large variation EPOR across observed. In vitro, rHuEPO had a protective effect radiation-treated cells (p<0.05), however treatment alone combined chemotherapy hypoxia did not influence survival. vivo, lung metastases immunocompromised mice injected relative (p<0.05). Conclusions: The lack an rhEPO highlights importance studies delineate effects process. These may begin uncover underlying explanation observed EPO-related decreased undergoing chemotherapy.

参考文章(55)
Jolanta Szenajch, Gabriel Wcislo, Jee-Yeong Jeong, Cezary Szczylik, Laurie Feldman, The role of erythropoietin and its receptor in growth, survival and therapeutic response of human tumor cells From clinic to bench - a critical review. Biochimica et Biophysica Acta. ,vol. 1806, pp. 82- 95 ,(2010) , 10.1016/J.BBCAN.2010.04.002
Domenico Ribatti, Marco Presta, Angelo Vacca, Roberto Ria, Roberta Giuliani, Patrizia Dell’Era, Beatrice Nico, Luisa Roncali, Franco Dammacco, Human Erythropoietin Induces a Pro-Angiogenic Phenotype in Cultured Endothelial Cells and Stimulates Neovascularization In Vivo Blood. ,vol. 93, pp. 2627- 2636 ,(1999) , 10.1182/BLOOD.V93.8.2627
O Miura, N Nakamura, FW Quelle, BA Witthuhn, JN Ihle, N Aoki, Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo Blood. ,vol. 84, pp. 1501- 1507 ,(1994) , 10.1182/BLOOD.V84.5.1501.BLOODJOURNAL8451501
Danny R. Welch, Technical considerations for studying cancer metastasis in vivo. Clinical & Experimental Metastasis. ,vol. 15, pp. 272- 306 ,(1997) , 10.1023/A:1018477516367
Angus M Sinclair, Marque D Todd, Kevin Forsythe, Susan J Knox, Steve Elliott, C Glenn Begley, None, Expression and function of erythropoietin receptors in tumors: implications for the use of erythropoiesis-stimulating agents in cancer patients. Cancer. ,vol. 110, pp. 477- 488 ,(2007) , 10.1002/CNCR.22832
Peter Vaupel, Debra K. Kelleher, Oliver Thews, Erythropoietin Restores the Anemia-induced Reduction in Cyclophosphamide Cytotoxicity in Rat Tumors Cancer Research. ,vol. 61, pp. 1358- 1361 ,(2001)
Tatsuma Okazaki, Satoru Ebihara, Masanori Asada, Shinsuke Yamanda, Kaijun Niu, Hiroyuki Arai, Erythropoietin Promotes the Growth of Tumors Lacking Its Receptor and Decreases Survival of Tumor-Bearing Mice by Enhancing Angiogenesis Neoplasia. ,vol. 10, pp. 932- 939 ,(2008) , 10.1593/NEO.08140
V. Moebus, H. Lueck, C. Thomssen, N. Harbeck, U. Nitz, R. Kreienberg, C. Jackisch, A. Schneeweiss, J. Huober, A. du Bois, M. Untch, The impact of epoetin-alpha on anemia, red blood cell (RBC) transfusions, and survival in breast cancer patients (pts) treated with dose-dense sequential chemotherapy: Mature results of an AGO phase III study (ETC trial) Journal of Clinical Oncology. ,vol. 25, pp. 569- 569 ,(2007) , 10.1200/JCO.2007.25.18_SUPPL.569
Geza Acs, Peter Acs, Susan M Beckwith, Richard L Pitts, Emily Clements, Kondi Wong, Ajay Verma, Erythropoietin and erythropoietin receptor expression in human cancer Cancer Research. ,vol. 61, pp. 3561- 3565 ,(2001)
Kenneth Jacobs, Charles Shoemaker, Richard Rudersdorf, Suzanne D. Neill, Randal J. Kaufman, Allan Mufson, Jasbir Seehra, Simon S. Jones, Rodney Hewick, Edward F. Fritsch, Makoto Kawakita, Tomoe Shimizu, Takaji Miyake, Isolation and characterization of genomic and cDNA clones of human erythropoietin Nature. ,vol. 313, pp. 806- 810 ,(1985) , 10.1038/313806A0