Regulation and function of the extracellular matrix protein tenascin-C in ovarian cancer cell lines

The extracellular matrix glycoprotein tenascin-C (TN) is overexpressed in t he stroma of malignant ovarian tumours particularly at the interface betwee n epithelia and stroma leading to suggestions that it may be involved in th e process of invasion (Wilson et al (1996) Br J Cancer 74: 999-1004). To de fine regulation of TN further and investigate its function in ovarian cance r, a range of cell line models were studied. Concentrations of secreted TN in media from cultures of ovarian fibroblast cell lines were at least 100-f old greater than from carcinoma cell lines. Evidence for paracrine regulati on of TN secretion was obtained by co-culture of carcinoma cells with fibro blast cells wherein secretion into the media was greater than from fibrobla sts alone. Transforming growth factor (TGF)-beta 1, insulin-like growth fac tor (IGF)-II and progesterone all stimulated TN secretion while human chori ogonadotropin (hCG), follicle-stimulating hormone (FSH) and gamma-interfero n inhibited secretion. TGF-beta 1 produced the greatest stimulation of TN i n cultured fibroblasts and its cc-expression with TN was examined in primar y ovarian tumours, There was a significant association between the presence of moderate-strong expression of TN and TGF-beta 1. Evidence for TN having a functional role in ovarian carcinoma was obtained from adhesion and migr ation assays. The PE01, PE04, SKOV-3 and 59M cell lines all demonstrated ma rked adhesion to plastic coated with TN relative to the control protein bov ine serum albumin (BSA) and expressed alpha 2 beta 1 and alpha 3 beta 1 int egrins, The SKOV-3 cell line migrated more rapidly through TN than through BSA indicating that TN can facilitate migration of ovarian carcinoma cells.