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
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 316卷 / 04期
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
相关论文
共 33 条
[11]   Involvement of tumor cell integrin αvβ3 in hematogenous metastasis of human melanoma cells [J].
Felding-Habermann, B ;
Fransvea, E ;
O'Toole, TE ;
Manzuk, L ;
Faha, B ;
Hensler, M .
CLINICAL & EXPERIMENTAL METASTASIS, 2002, 19 (05) :427-436
[12]   REQUIREMENT OF THE NPXY MOTIF IN THE INTEGRIN BETA-3 SUBUNIT CYTOPLASMIC TAIL FOR MELANOMA CELL-MIGRATION IN-VITRO AND IN-VIVO [J].
FILARDO, EJ ;
BROOKS, PC ;
DEMING, SL ;
DAMSKY, C ;
CHERESH, DA .
JOURNAL OF CELL BIOLOGY, 1995, 130 (02) :441-450
[13]   DISRUPTION OF EPITHELIAL CELL-MATRIX INTERACTIONS INDUCES APOPTOSIS [J].
FRISCH, SM ;
FRANCIS, H .
JOURNAL OF CELL BIOLOGY, 1994, 124 (04) :619-626
[14]   Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death [J].
Hazlehurst, LA ;
Landowski, TH ;
Dalton, WS .
ONCOGENE, 2003, 22 (47) :7396-7402
[15]   Role of integrins in cell invasion and migration [J].
Hood, JD ;
Cheresh, DA .
NATURE REVIEWS CANCER, 2002, 2 (02) :91-+
[16]   Integrin αvβ3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells [J].
Kozlova, NI ;
Morozevich, GE ;
Chubukina, AN ;
Berman, AE .
ONCOGENE, 2001, 20 (34) :4710-4717
[17]  
Kozlova NI, 1997, BIOCHEM MOL BIOL INT, V43, P529
[18]  
LAING NM, 1997, ENCY CANC, V1, P560
[19]   Activation of metalloproteinases and their association with integrins: an auxiliary apoptotic pathway in human endothelial cells [J].
Levkau, B ;
Kenagy, RD ;
Karsan, A ;
Weitkamp, B ;
Clowes, AW ;
Ross, R ;
Raines, EW .
CELL DEATH AND DIFFERENTIATION, 2002, 9 (12) :1360-1367
[20]   Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness [J].
Liang, Y ;
Meleady, P ;
Cleary, I ;
McDonnell, S ;
Connolly, L ;
Clynes, M .
EUROPEAN JOURNAL OF CANCER, 2001, 37 (08) :1041-1052
1234