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

Insulin-like growth factor-I (IGF-I) 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-I 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-I and IGF-I type I receptor (IGF-IR) in 50 paired normal colon and carcinoma samples. IGF-IR mRNA was present in all samples, whereas IGF-I mRNA was detected in only 30 normal (60%) and 27 tumour (54%) biopsies. Samples that did not express IGF-I mRNA had no IGF-I 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-I mRNA levels and microvessel density in the colorectal cancers.