Expression and Role of Integrins in Invasive Activity of Oncotransformed Fibroblasts Differing in Spontaneous Metastasizing

G. E. Morozevich, N. I. Kozlova, A. N. Chubukina, I. A. Eltsov, and A. E. Berman^*

Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, ul. Pogodinskaya 10, Moscow 119121, Russia; fax: (7-095) 245-0857; E-mail: berman@ibmh.msk.su

^* To whom correspondence should be addressed.

Received August 14, 2003; Revision received October 7, 2003

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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.

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KEY WORDS: integrins, extracellular matrix, metastasizing, invasion

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