Multidrug-resistant tumor cells with decreased malignancy:: a role for integrin αvβ3

被引:10
作者
Kozlova, NI
Morozevich, GE
Shtil, AA
Berman, AE
机构
[1] VN Orekhovich Inst Biomed Chem, Moscow 119121, Russia
[2] NN Blokhin Canc Ctr, Moscow 115478, Russia
基金
俄罗斯基础研究基金会;
关键词
integrins; extracellular matrix; multidrug resistance; invasion; metastasis;
D O I
10.1016/j.bbrc.2004.03.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:1173 / 1177
页数:5
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