Multidrug-resistant tumor cells with decreased malignancy: a role for integrin alphavbeta3 |
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Authors: | Kozlova Nadezhda I Morozevich Galina E Shtil Alexander A Berman Albert E |
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Affiliation: | V.N. Orekhovich Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, Russia. |
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Abstract: | We studied whether acquisition of multidrug resistance (MDR) by tumor cells can alter their integrin profile and malignant behavior. Hamster fibroblast cell line HET-SR-2SC-LNM was selected for MDR, yielding the 2SC/20 subline. Compared with the parental cells, the 2SC/20 subline weakly adhered to denatured collagen (dCol) which correlated with decreased expression of alphavbeta3, a dCol receptor. Importantly, 2SC/20 subline demonstrated significantly decreased activity of collagenase MMP-2, lower ability to invade Matrigel, and attenuated metastasis in syngeneic animals. We provide evidence for the first time that selection for MDR can be associated with down-regulation of alphavbeta3 integrin, supporting our recent proof of the pro-apoptotic role of this integrin (Oncogene 20 (2001) 4710). Lack of alphavbeta3 expression may link cell survival under toxic conditions with decreased malignancy of the resulting drug resistant tumor. |
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Keywords: | Integrins Extracellular matrix Multidrug resistance Invasion Metastasis |
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