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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Damiano, J. S. Articles by Dalton, W. S. Search for Related Content PubMed PubMed Citation Articles by Damiano, J. S. Articles by Dalton, W. S. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 5 (March 1), 1999: pp. 1658-1667 Cell Adhesion Mediated Drug Resistance (CAM-DR): Role of Integrins and Resistance to Apoptosis in Human Myeloma Cell Lines Jason S. Damiano, Anne E. Cress, Lori A. Hazlehurst, Alexander A. Shtil, and William S. Dalton From the H. Lee. Moffitt Cancer Center, University of South Florida, Tampa, FL; and the Arizona Cancer Center, University of Arizona, Tucson, AZ. Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug exposure may differ from drug resistance mechanisms selected for by chronic drug exposure. We show here that drug-sensitive 8226 human myeloma cells, demonstrated to express both VLA-4 (41) and VLA-5 (51) integrin fibronectin (FN) receptors, are relatively resistant to the apoptotic effects of doxorubicin and melphalan when pre-adhered to FN and compared with cells grown in suspension. This cell adhesion mediated drug resistance, or CAM-DR, was not due to reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members. As determined by flow cytometry, myeloma cell lines selected for drug resistance, with either doxorubicin or melphalan, overexpress VLA-4. Functional assays revealed a significant increase in 4-mediated cell adhesion in both drug-resistant variants compared with the drug-sensitive parent line. When removed from selection pressure, drug-resistant cell lines reverted to a drug sensitive and 4-low phenotype. Whether VLA-4-mediated FN adhesion offers a survival advantage over VLA-5-mediated adhesion remains to be determined. In conclusion, we have demonstrated that FN-mediated adhesion confers a survival advantage for myeloma cells acutely exposed to cytotoxic drugs by inhibiting drug-induced apoptosis. This finding may explain how some cells survive initial drug exposure and eventually express classical mechanisms of drug resistance such as MDR1 overexpression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Ikeda, T. Hideshima, M. Fulciniti, R. J. Lutz, H. Yasui, Y. Okawa, T. Kiziltepe, S. Vallet, S. Pozzi, L. Santo, et al. The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells In vitro and In vivo Clin. Cancer Res., June 15, 2009; 15(12): 4028 - 4037. [Abstract] [Full Text] [PDF] B. Nervi, P. Ramirez, M. P. Rettig, G. L. Uy, M. S. Holt, J. K. Ritchey, J. L. Prior, D. Piwnica-Worms, G. Bridger, T. J. Ley, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100 Blood, June 11, 2009; 113(24): 6206 - 6214. [Abstract] [Full Text] [PDF] M. Niedermeier, B. T. 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