Interleukin-6 increases expression of serine protease inhibitor Kazal type 1 through STAT3 in colorectal adenocarcinoma.

摘要: Inflammation promotes colorectal cancer (CRC) tumorigenesis, but the underlying molecular mechanisms are still being uncovered. Proinflammatory cytokine interleukin-6 (IL-6) stimulates survival signaling in CRC; inflammatory signals also regulate production and activity of proteases their inhibitors. Over-expression serine protease inhibitor Kazal type 1 (SPINK1) predicts an unfavorable outcome colon cancer. The SPINK1 gene contains IL-6 responsive element, suggesting it could act as acute phase reactant. We assessed connection between SPINK1, function mechanism this signaling. Our results show that Colo205 HT-29 cells express secrete both fibroblast-derived recombinant further increased levels. Concurrently CRC augmented fibroblasts. In tissues were positive for whereas was found stromal cells. stimulated secretion trypsin-1 -2, key targets inhibition, -2 levels remained constantly low. Functionally, motility Mechanistically, activated canonical STAT3 pathway inhibition phosphorylation decreased -2. Taken together, our indicate a novel link originating from tumor microenvironment This finding has potential therapeutic implications targeted therapy, confirms acts reactant participates paracrine crosstalk with © 2015 Wiley Periodicals, Inc.