Osteopontin Expression may be induced by c-Src in Papillary Thyroid Carcinoma

Y Kato, PhD, a H Zhu, MD,a,b, R Tanaka, MD,a T Obara, MD,a K Sato, MD,a T Sawada, MD,a M Kobayashi, MD,a

aTokyo Women's Medical University, Shinjuku, Tokyo JapanDepartment of General Surgery, First bAffiliated Hospital of Anhui Medical University,, Anhui, China

AIM: Osteopontin (OPN), a secreted adhesive glycoprotein, is significantly overexpressed in a variety of malignant tumors. Moreover, increased levels of OPN have been detected in the blood of patients with metastatic carcinoma. On immunohistochemical examination, OPN was shown to be expressed in papillary thyroid carcinoma. We investigated the mechanisms of the induction of OPN expression in papillary thyroid carcinoma. METHODS: We examined the expression of c-src and OPN in 30 cases of papillary thyroid carcinoma by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. RESULTS: Each of 5 cases studied by Northern and Western blotting analyses revealed substantial increases of c-src and OPN mRNA and protein levels in tumor areas as compared with surrounding normal thyroid tissues. Moreover, signals of c-src and OPN mRNA were detected in both infiltrating mononuclear cells and tumor cells by in situ hybridization. Immunohistochemical localizations of c-Src and OPN proteins were the same as those of transcripts described above. CONCLUSIONS: These results suggested that the induction of the expression of OPN invasiveness in papillary thyroid carcinoma was one of the important down stream event of increased c-Src expression.

KEY WORDS: Osteopontin, c-Src, Papillary thyroid carcinoma.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.