Role of stromal thrombospondin-1 in motility and proteolytic activity of oral squamous cell carcinoma cells.
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.
Hayashido
Yasutaka
Y
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
Nakashima
Masahiro
M
Urabe
Kazuhiko
K
Yoshioka
Hideo
H
Yoshioka
Yukio
Y
Hamana
Tomoaki
T
Kitano
Hisataka
H
Koizumi
Koh-Ichi
K
Okamoto
Tesuji
T
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D011233:Precipitin Tests; D019700:Thrombospondin 1 / Q000096:biosynthesis*; D013997:Time Factors
D017077:Culture Media, Conditioned; D019700:Thrombospondin 1