Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis.

摘要: Purpose: The purpose of this study was to identify a mediator produced by human colon cancer cells that is responsible for the induction hyperplasia in adjacent mucosa. Experimental Design: Seventy surgical specimens were immunostained determine presence cytokines can induce mucosal. Human with low and high metastatic potential implanted into cecal wall nude mice. resulting lesions studied immunohistochemistry detect possible mediators mucosal hyperplasia. Results: Immunostaining 70 from patients suggested distant metastasis associated expression interleukin (IL)-15 and, lesser extent, transforming growth factor α. production IL-15 not infiltration natural killer tumors. Cecal tumors mice (KM12C KM12SM cells, respectively) expressed similar levels α, detected only surrounding receptor rat intestinal epithelial (IEC6 cells) confirmed immunoblotting antibodies against α IL-2 β γ subunits binding assay using 125I-labeled (Kd = 0.011 nm). stimulated proliferation IEC6 even under serum starvation. Treatment decreased doxorubicin-mediated cytotoxicity. In treated either IL-15- or KM12SM-conditioned medium, revealed decrease p21Waf1, Bax, Bak an increase cyclin E, proliferating cell nuclear antigen, phosphorylated active form AKT, basic fibroblast factor, vascular endothelial changes growth, survival, angiogenesis. Conclusions: These data indicate carcinoma mucosa cancer, thus contributing angiogenesis progression disease.