Modulation of prostate cancer cell attachment to matrix by Versican

Abstract

In this study, we examined whether versican, a recognized anti-cell adhesive molecule for various mesenchymal and nerve cell types, influences prostate cancer cell adhesion to extracellular matrix components. Prostate cancer cell adhesion to fibronectin, a major component of the stromal extracellular matrix was inhibited by versican-rich conditioned medium (CM) from cultured human prostatic fibroblasts. In contrast, cancer cell attachment to laminin, a component of basement membranes, was not affected by the same CM. Consistent with versican being the active inhibitory factor in the CM, the integrity of chondroitin sulfate side chains and an ability to bind the RGD (Arg-Gly-Asp) peptide sequence of fibronectin were essential for the inhibition of prostate cancer cell attachment to fibronectin. Subsequent studies with versican purified from human prostate fibroblast CM confirmed its anti-adhesive activity. We conclude that versican is an important modulator of tumor cell attachment to the interstitial stromal matrix of the prostate, the latter being an essential step in cancer cell motility and local invasion of the prostatic stroma.