Dual function of transforming growth factor beta 2 in the progression of gastric carcinoma.

BACKGROUND: It has been reported that transforming growth factor beta (TGFβ) might play an important role for the development of various types of carcinomas. TGFβ is produced from not only cancer cells but also stromal cells such as fibroblasts. Controversial functions of TGFβ for tumor progression such as tumor suppression and progression has been widely recognized. TGFβ has 3 subtypes including TGFβ1, TGFβ2, and TGFβ3. The role of TGFβ1 and TGFβ3 for gastric carcinoma (GC) progression has been well-known, but that of TGFβ2 remains to be unknown. AIM: To clarify the significance of TGFβ2 in the development of GC. METHODS: Immunohistochemical analysis of GC was performed to clarify the clinical function of TGFβ2 on the progression of GC by evaluating TGFβ2 expression on both cancer cells and cancer-associated fibroblasts (CAFs) using 518 GC specimens. RESULTS: High TGFβ2 expression in cancer cells was significantly correlated with T factor and stage, but not with vascular invasion and lymphatic invasion. In contrast, TGFβ2 expression on CAFs was significantly correlated with lymph node metastasis and vascular invasion, but not with the T factor. Five-year survival of patients with TGFβ2-high on cancer cells and -low on CAFs was significantly worse in compared to the other group These findings suggest that TGFβ2 might play differential roles between cancer cells and CAFs in the development of GC. CONCLUSION: TGFβ2 on cancer cells might stimulates the cancer proliferation and invasion, but not TGFβ2 on CAFs. TGFβ2 high on cancer cells and low on CAF or others might be a promising prognostic factor for patients with GC.