Site-dependent production of transforming growth factor β1 in colonic mucosa: Its possible role in tumorigenesis of the colon

Abstract

Transforming growth factor (TGF) β1 has an antitumorigenic role in the gastrointestinal tract and may be associated with the development of colon neoplasia. In the present study we investigated whether TGF-β1 production in mucosa is lower in the distal colon, which is where clinical evidence shows that the incidence of colon neoplasia is higher, and whether TGF-β1 levels were lower in the mucosa of patients with colon adenoma. Production of colon mucosa TGF-β1 was investigated by means of a 24-hour organ culture with biopsy specimens taken from different segments of the colon of 58 normal subjects by using an enzyme immunoassay. TGF-β1 production in colon mucosa from locations near the site of sporadic adenoma was also investigated in 46 patients. TGF-β1 production gradually increased from the rectum to the ascending colon in a statistically significant manner in both normal (r = 0.77, P <.0001) and adenoma-bearing (r = 0.8, P <.0001) mucosa. When TGF-β1 production was compared between normal and adenoma-bearing mucosa, levels were lower in the latter, although statistically significant results were seen only in the transverse colon (P <.05). TGF-β1 production has clear site dependency, being lowest in the rectum and highest in the ascending colon. Furthermore, low levels of TGF-β1 are associated with the development of adenoma. Our results suggest the possibility that this site dependency is associated with the higher epidemiologic incidence of colon neoplasia in the distal colon. (J Lab Clin Med 2000;136:201-8)