PURPOSE: Transforming growth factor-beta1 (TGF-β1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-β1 in invasion and metastasis in gastric cancer. MATERIALS AND METHODS: We detected TGF-β1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-β1 levels in the peripheral vein and in the tumor drainage vein were assayed. RESULTS: In the cytoplasm of cancer cells, TGF-β1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-β1–negative primary tumor, metastatic lymph nodes were positive for TGF-β1 staining in 32 cases (54.2%). Positive staining of TGF-β1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-β1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-β1 did not differ between TGF-β1–negative and –positive groups. There were also no differences in plasma TGF-β1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings. CONCLUSION: Transforming growth factor-β1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-β1 in the tumor does not contribute to the total amount of TGF-β1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-β1 alters the biologic behavior of the tumor.
Transforming growth factor-β1 induces connective tissue growth factor expression and promotes peritoneal metastasis of gastric cancer