Induction of angiogenesis by hyperplastic colonic mucosa adjacent to coloncancer

We determined whether hyperplastic mucosa adjacent to colon cancer contribu tes to neoplastic angiogenesis. Surgical specimens of human colon cancer (4 0 Dukes' stage B and 34 Dukes' stage C) were analyzed by immunohistochemist ry for expression of proliferative and angiogenic molecules, The mucosa adj acent to Dukes' stage C tumors (but not Dukes' stage B tumors) had a higher Ki-67 labeling index and a higher expression of epidermal growth factor re ceptor and transforming growth factor-alpha than distant mucosa, The expres sion levels of vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8, and the vascular density in the adjacent mucosa were similar to those in the tumor lesions and significantly higher than those in the distant mucosa, The expression of interferon-beta inversely correlat ed with the level of pro-angiogenic molecules and the vascular density. The injection of metastatic human colon cancer cells and murine colon cancer c ells into the cecal wall of mice Induced hyperplastic changes in the adjace nt mucosa which expressed higher levels of epidermal growth factor receptor , basic fibroblast growth factor, and vascular endothelial growth factor, a nd lower levels of interferon-beta than did the control mucosa, which direc tly correlated with the degree of hyperplasia, These data suggest that meta static human colon cancer cells can induce hyperplasia in the adjacent muco sa, which in turn produces angiogenic molecules that contribute to neoplast ic angiogenesis,