CYTOKINE-PRODUCING FUNCTION OF IMMUNOCOMPETENT BLOOD CELLS AND ITS INTERRELATIONS WITH HEPARANASE-1 EXPRESSION IN GASTRIC CARCINOGENESIS

The aim of present study was to investigate relationships between cytokine-producing potential of immunocompetent blood cells (ICC), and expression of heparanase-1 in stomach adenomas and adenocarcinomas. Cytokine-producing potential of ICC, both spontaneous and induced by polyclonal activators, was studied in peripheral blood of thirty-two patients with adenomas and thirty-six patients with gastric adenocarcinoma. Appropriate values were expressed as an influence index of polyclonal activators (IIPA) upon the cytokine production. In subjects with gastric adenomas, the IIPA indexes based on IL-1ra, ТNFα, IL- 18, and IFNγ production proved to exceed similar parameters for the patients with adenocarcinomas. Expression of heparanase-1 in epithelium of adenomas varied from 0.27 to 3.00. Similar values for adenomatous stroma varied between 2.27 and 11.48. Meanwhile, the variation limits for heparanase-1 expression in adenocarcinomas (as percentage of specifically stained area) were quite considerable (1.79 to 14.26), due to inclusion of adenocarcinomas at variable differentiation stages. Indexes of heparanase-1 expression were shown to be in direct correlation with numbers of regional lymph node metastases. Multivariate analysis revealed a canonical correlation between the levels of heparanase-1 expression in adenomatous epithelium, and IIPA effects upon production of IL-2, IL-6 and IL-8, as well as with effects of IIPA upon production of IL-18, IL-18BP, and IL-8. A canonical correlation was also noted between the heparanase-1 expression in stroma of adenomas, and IIPA upon IL-1ra, TNFα, IL-18 production. The data suggest an involvement of molecular and cellular mechanisms, mediated by cytokines and heparanase-1, thus providing a common vector promoting tumor progression