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

Abstract

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.

• Authors: G E Morozevich, N I Kozlova, A N Chubukina, I A Eltsov, A E Berman
• Journal: Biochemistry. Biokhimiia (Biochemistry (Mosc)) Vol. 69 Issue 6 Pg. 665-73 (Jun 2004) ISSN: 0006-2979 [Print] United States
• PMID: 15236606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Integrins
• Oligopeptides
• arginyl-glycyl-aspartic acid
• Matrix Metalloproteinase 2

Topics

• Animals
• Avian Sarcoma Viruses (physiology)
• Cell Adhesion (drug effects)
• Cell Line, Transformed
• Cell Transformation, Viral (drug effects)
• Cricetinae
• Extracellular Matrix Proteins (metabolism)
• Fibroblasts (enzymology, metabolism, pathology, virology)
• Gene Expression
• Integrins (antagonists & inhibitors, metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Neoplasm Metastasis (pathology)
• Oligopeptides (pharmacology)
• Signal Transduction