Differential localization of transforming growth factor-β isoforms in human gastric mucosa and overexpression in gastric carcinoma

Transforming growth factor β (TGF-β) isoforms comprise a family of multifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. We examined TGF-β expression in normal human gastric mucosa and carcinoma. The distribution and expression of TGF-β isoforms in 4 normal mucosa samples from organ donors, in 12 normal mucosa samples adjacent to gastric cancer and in 12 gastric carcinomas were examined using immunohistochemistry and Northern blot analysis. Because TGF-βs regulate collagen expression, collagen type I α₁ mRNA amounts were also examined. Immunohistochemical analysis of normal human gastric tissue samples indicated that TGF-β₁ localized principally in parietal cells but also in some surface mucus cells, TGF-β₂ was present exclusively in chief cells and TGF- β₃ was present in parietal, chief and mucus cells. In the gastric cancers, strong colocalization of TGF-β₁, -β₂ and -β₃ was evident in the cancer cells. Northern blot analysis indicated that, compared to normal gastric tissue, gastric cancers showed a 4.8- and 6-fold increase in mRNA amounts encoding TGF-β₁ and TGF-β₃, respectively. In contrast, TGF-β₂ mRNA amounts were comparable in both groups. Northern blot analysis showed a 10- fold increase in human collagen type I α₁ mRNA amounts compared to normal gastric tissue. These findings imply a role for TGF-βs in normal human gastric mucosa function, and raise the possibility that the aberrant colocalization and overexpression of all 3 TGF-β isoforms in human gastric cancer cells in vivo may contribute to the pathobiology of gastric carcinoma.