Local expression of insulin-like growth factor-I affects angiogenesis in colorectal cancer

Insulin-like growth factor-1 (IGF-1) has potent mitogenic and anti-apoptotic effects that give it a critical role in the regulation of rapidly renewing epithelial cell populations such as those found in the colon. Recent evidence has implicated circulating IGF-1 levels as an important determinant of colorectal cancer risk, but the role, if any, of its autocrine/paracrine expression remains unexplored. Therefore, we investigated the local expression of IGF-1 and IGF-1 type I receptor (IGF-IR) in 50 paired normal colon and carcinoma samples. IGF-IR mRNA was present in all samples, whereas IGF-1 mRNA was detected in only 30 normal (60%) and 27 tumour (54%) biopsies. Samples that did not express IGF-1 mRNA had no IGF-1 peptide detectable by immunocytochemistry. The absence of local IGF-1 expression was associated with significantly reduced mRNA levels specifying the proliferating cell nuclear antigen and c-myc, as well as Cox-2, and vascular endothelial growth factor - gene products that regulate angiogenesis. The biological relevance of this finding is suggested by the significant association between local IGF-1 mRNA levels and microvessel density in the colorectal cancers. Copyright (C) 2002 S KargerAG, Basel.