Multidrug-resistant tumor cells with decreased malignancy: a role for integrin alphavbeta3.
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.
Kozlova
Nadezhda I
NI
V.N. Orekhovich Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, Russia.
Morozevich
Galina E
GE
Shtil
Alexander A
AA
Berman
Albert E
AE
D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D018432:Drug Resistance, Multiple; D005109:Extracellular Matrix / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D001357:Sarcoma, Avian / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary
D039302:Integrin alphaVbeta3; D020778:Matrix Metalloproteinase 2