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The distribution of alkaline phosphatase (ALP) activity in neoplastic lesions of the rat stomach was examined by histochemistry and electron microscopic cytochemistry, and its isoenzyme activity was biochemically determined in an experimental model of gastric carcinogenesis using N-methyl-N-nitrosourea (MNU). In addition, [3H]1, 25-dihydroxyvitamin D3 (1, 25(OH)2D3) binding activity into the gastric lesions was assayed. Histochemical positive reaction for ALP was conspicuous exclusively in the fibrous stroma of both intramucosal neoplastic lesions and invasive adenocarcinomas in the glandular stomach. Ultracytochemical examinations revealed that the reaction product of ALP activity was present on the plasma membrane of fibroblasts adjacent to neoplastic cells and collagenous matrices beneath the latter cells. Biochemically, the major component of total ALP activity, which showed 25- to 33-fold increase in advanced carcinomas as compared with the normal glandular stomach, was found to be of tissue-unspecific (bone/liver/kidney) type, while the intestinal isoenzyme formed a minor proportion. Extraordinarily increased binding activity of 1, 25(OH)2D3 to carcinomas appeared consistent with marked production of ALP in the stroma of neoplastic lesions in the present study. The preferential localization of enhanced ALP activity in the fibrous stroma of neoplasms may be involved in some epithelial-stromal interactions or signal transduction mechanism during gastric carcinogenesis.

ENHANCEMENT OF STROMAL ALKALINE PHOSPHATASE ACTIVITY IN N-METHYL-N-NITROSOUREA-INDUCED ADENOCARCINOMA OF THE RAT STOMACH