Expression and role of integrins in invasive activity of oncotransformed fibroblasts differing in spontaneous metastasizing

• Published in: Biochemistry (Moscow) Vol. 69; no. 6; pp. 665 - 673
• Main Authors: Morozevich, G E, Kozlova, N I, Chubukina, A N, Eltsov, I A, Berman, A E
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.06.2004
• Subjects: Animals; Avian Sarcoma Viruses - physiology; Cell Adhesion - drug effects; Cell Line, Transformed; Cell Transformation, Viral - drug effects; Cricetinae; Extracellular Matrix Proteins - metabolism; Fibroblasts - enzymology; Fibroblasts - metabolism; Fibroblasts - pathology; Fibroblasts - virology; Gene Expression; Integrins - antagonists & inhibitors; Integrins - metabolism; Matrix Metalloproteinase 2 - metabolism; Neoplasm Metastasis - pathology; Oligopeptides - pharmacology; Proteins; Signal Transduction
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1023/B:BIRY.0000033740.76015.47

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.