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 the stroma of malignant ovarian tumours particularly at the interface between epithelia and stroma leading to suggestions that it may be involved in the process of invasion (Wilson et al (1996) Br J Cancer 74: 999-1004). To define regulation of TN further and investigate its function in ovarian cancer, 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-fold greater than from carcinoma cell lines. Evidence for paracrine regulation of TN secretion was obtained by co-culture of carcinoma cells with fibroblast cells wherein secretion into the media was greater than from fibroblasts alone. Transforming growth factor (TGF)-beta1, insulin-like growth factor (IGF)-II and progesterone all stimulated TN secretion while human choriogonadotropin (hCG), follicle-stimulating hormone (FSH) and gamma-interferon inhibited secretion. TGF-beta1 produced the greatest stimulation of TN in cultured fibroblasts and its co-expression with TN was examined in primary ovarian tumours. There was a significant association between the presence of moderate-strong expression of TN and TGF-beta1. Evidence for TN having a functional role in ovarian carcinoma was obtained from adhesion and migration assays. The PE01, PE04, SKOV-3 and 59M cell lines all demonstrated marked adhesion to plastic coated with TN relative to the control protein bovine serum albumin (BSA) and expressed alpha2beta1 and alpha3beta1 integrins. The SKOV-3 cell line migrated more rapidly through TN than through BSA indicating that TN can facilitate migration of ovarian carcinoma cells.
Wilson
K E
KE
ICRF Medical Oncology Unit, Western General Hospital, Edinburgh, UK.
Bartlett
J M
JM
Miller
E P
EP
Smyth
J F
JF
Mullen
P
P
Miller
W R
WR
Langdon
S P
SP
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016023:Integrins / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000494:pharmacology; D020033:Protein Isoforms; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D019063:Tenascin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006063:Chorionic Gonadotropin; D016023:Integrins; D020033:Protein Isoforms; D019063:Tenascin; D016212:Transforming Growth Factor beta; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D005640:Follicle Stimulating Hormone