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Title: The expression and role of the extracellular matrix protein tenascin in ovarian cancer
Author: Wilson, Katherine Elizabeth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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In order to determine which cell types were capable of producing TN, in vitro, fibroblast cells, cultured from ascitic fluids of ovarian cancer patients, and established ovarian carcinoma cell lines were studied. TN levels in conditioned media were measured by ELISA. "Basal" levels of TN secretion were determined by culturing cells in serum-free media; under these conditions the ovarian fibroblasts secreted levels of TN over 100 fold greater than the epithelial cells. To examine whether a paracrine interaction between the fibroblast and epithelial cells can influence TN production, the cells were co-cultured in compartments separated by a filter, which allowed diffusion of soluble factors. The co-cultured populations of cells produced significantly more TN than either cell type alone. The effects of a number of potential modulating factors, on secretion of TN, have been investigated. Several factors (IGF II, TGFβ, progesterone and EGF) stimulate TN secretion by fibroblasts while other factors (gonadotrophins and interferon) inhibit TN secretion in the same cell type. Of the factors studied TGF-β provided the greatest induction of TN in fibroblasts. None of these factors induced the PEO1 epithelial cell line to produce measurable levels of TN. Adhesion and migration assays were used to examine how ovarian carcinoma cell lines interacted with TN, as compared with the ECM proteins fibronectin and collagen IV. The assays demonstrated that TN promoted cell adhesion, spreading and migration in the SKOV-3, 59M, PEO1 and PEO4 ovarian carcinoma cell lines, however, fibronectin and collagen IV appeared to be preferable substrates. These studies have demonstrated that TN is overexpressed in malignant ovarian tumours, and paracrine growth factors, such as TGFβ can induce the synthesis of TN in ovarian fibroblasts. Tumour cells can adhere to, and migrate on TN. These data would be consistent with TN playing a role in the invasion and metastasis of ovarian cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available