title: Multidrug-resistant tumor cells with decreased malignancy: a role for integrin alphavbeta3.
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.
authors.affiliation: V.N. Orekhovich Institute of Biomedical Chemistry, 10 Pogodinskaya Street, 119121 Moscow, Russia.
authors.forename: Nadezhda I
authors.initials: NI
authors.lastname: Kozlova
authors.forename: Galina E
authors.initials: GE
authors.lastname: Morozevich
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
authors.forename: Albert E
authors.initials: AE
authors.lastname: Berman
mesh_terms: 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
chemical_list: D039302:Integrin alphaVbeta3; D020778:Matrix Metalloproteinase 2