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Int J Mol Med. 2003 Oct;12(4):447-52.

Role of stromal thrombospondin-1 in motility and proteolytic activity of oral squamous cell carcinoma cells.

Author information

1
Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. hayashiy@hiroshima-u.ac.jp

Abstract

The immunohistochemical localization of thrombospondin-1 (TSP-1) in human normal oral mucosa and oral squamous cell carcinoma (SCC) was examined. The immunostaining of TSP-1 was mainly localized in the connective tissues adjacent to the epithelium of oral mucosa, whereas epithelial cells showed negligible immunoreactivity for TSP-1. TSP-1 expression was striking in the stroma of SCC. TSP-1 synthesis by SCC cells and fibroblasts in culture was examined by immunoprecipitation with anti-TSP-1 antibody. Fibroblasts produced a large amount of TSP-1, whereas SCC cells secreted little amount of TSP-1. Treatment of fibroblasts by the conditioned medium of SCC cells led to an increase in TSP-1 synthesis. TSP-1 induced haptotactic migration and stimulated the production of matrix metalloproteinase-9 (MMP-9) in SCC cells. These results suggest that TSP-1 in the stroma of oral SCC might be synthesized by mesenchymal cells but not by epithelial cells, and that the synthesis of TSP-1 might be regulated by interaction with SCC cells. TSP-1 accumulated in the stroma might promote the progression of oral SCC by enhancing the motility and proteolytic activity in a paracrine manner.

PMID:
12964017
[Indexed for MEDLINE]

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