Overexpression of Latent Transforming Growth Factor‐βl (TGF‐βl) Binding Protein 1 (LTBP‐1) in Association with TGF‐β1 in Ovarian Carcinoma

Using the differential display method, latent transforming growth factor‐β (TGF‐β1) binding protein 1 (LTBP‐1) mRNA was identified as one of the enriched mRNAs in ovarian carcinoma tissues after isolation of genes responsible for the development of ovarian cancer. Semi‐quantitative reverse transcription (RT)‐PCR analysis showed that expression of LTBP‐1 and TGF‐β1 mRNAs was much higher in both serous and mucinous adenocarcinomas than in their benign counterparts, including serous and mucinous cystadenomas and cystadenomas of low malignant potential (LMPs). Immunohistochemical analysis demonstrated that only proliferating benign adenoma cells were immunoreactive for both LTBP‐1 and TGF‐β1 proteins. In contrast, most serous and mucinous adenocarcinoma cells and their surrounding stroma were intensely immunoreactive for LTBP‐1 and TGF‐β1. LTBP‐1 and TGF‐β1 proteins, and their complex forms were identified in ovarian carcinoma cell lines and in their culture media by western blot analysis, suggesting these products were produced in ovarian carcinoma cells. RT‐PCR analysis demonstrated that LTBP‐1L, one of the LTBP‐1 transcripts that has a strong activity in targeting the latent form of TGF‐β1 to extracellular matrix (ECM), was predominantly expressed in ovarian carcinomas. Taken together, the results suggest that upregulation of LTBP‐1 in ovarian carcinoma cells may have an important role in distributing TGF‐β1 in the stromal tissues surrounding carcinoma cells.