The interaction of tenascin-C with fibronectin modulates the migration and specific metalloprotease activity in human mesothelioma cell lines of different histotype

Abstract

Malignant mesothelioma (MM) is a tumor with local invasive behaviour. Tenascin-C (TN-C) with fibronectin (FN) are associated extracellular matrix (ECM) molecules frequently neo-expressed in stromal remodeling during neoplastic progression, mostly at the invasive edge of these tumors. Tenascin-C alone or in association with other ECM molecules, could play an important role in the process of tumor invasion, acting as substrate for movement or modulating the migration on FN or promoting the degradation of ECM. Three mesothelioma cell lines of different histotype were analysed for the adhesive capacity on TN-C. The haptotactic activity on TN and the TN modulation of migration on a substrate of FN were analysed by a Boyden modified chamber. The effects of TN on proteolytic activity was evaluated by zymography. None of the lines adhered to tenascin. TN-C was not haptotactic for the three cell lines. Soluble or solid TN reduced the migration on FN of epithelial (E-MM) and sarcomatous cell line (S-MM), whereas enhanced the movement of a byphasic cell line (B-MM). When the cells were pretreated with anti-integrin blocking antibodies we observed a different pattern of inhibition of migration on FN respect to FN plus TN. Finally, no difference of metalloprotease (MMP-2, MMP-3, MMP-7, MMP-9) activity was observed between cells plated on FN and on FN plus TN, except for B-MM which showed an increased MMP-7 activity when TN was added to FN. Although TN is not a substrate for movement of MM cell lines, it interacts with FN by modulating differently the migration, according to the different histotype and to the integrin involved, and increasing specific metalloprotease activity.