Expression and role of integrins in invasive activity of oncotransformed fibroblasts differing in spontaneous metastasizing.
Four closely related lines of RSV-transformed Syrian hamster fibroblasts differing drastically in their spontaneous metastatic capacity were investigated for the surface expression of integrins, in vitro invasion, and production of MMP-2 collagenase. The highly metastasizing HET-SR-2SC-LNM cells differ from the lowly metastasizing parental HET-SR cells in a high level of the surface expression of the collagen-specific alpha1beta1, alpha2beta1, and alphavbeta3 integrins, a high invasive activity, and an increased production of MMP-2. The same properties are characteristic for the actively metastasizing cells of the independent HET-SR-1 line. The lowly metastasizing fibroblasts that are derived from HET-SR-2SC-LNM retain a high level of the expression of the alpha1beta1 and alpha2beta1 integrins, but, unlike the parental line, they exhibit a decreased expression of the alphavbeta3 integrin, invasion in Matrigel, and MMP-2 production. Substrate stimulation of the signal function of the collagen-specific integrins increases the production of MMP-2 by the metastatically active fibroblasts. Inhibition of the signal activity of the integrins by RGD-containing pentapeptide or by genistein reduces markedly in vitro invasion in Matrigel and MMP-2 production. The role of specific properties of the extracellular matrix surrounding tumor cells and of specific surface integrins expressed in these cells in developing of the malignant phenotype is discussed.
Morozevich
G E
GE
Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow 119121, Russia. berman@ibmh.msk.su
Kozlova
N I
NI
Chubukina
A N
AN
Eltsov
I A
IA
Berman
A E
AE
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects; D006224:Cricetinae; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D015870:Gene Expression; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D015398:Signal Transduction
D016326:Extracellular Matrix Proteins; D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020778:Matrix Metalloproteinase 2