Expression of hypoxia‐inducible factor‐1α is associated with tumor vascularization in human colorectal carcinoma

Abstract

HIF‐1 is reported to transactivate expression of VEGF, which is an important angiogenic factor. To determine whether HIF‐1α plays a role in angiogenesis through its regulation of VEGF, we examined expression of HIF‐1α and its relation to clinicopathologic features, VEGF expression and prognosis of patients with colorectal carcinoma. Expression of HIF‐1α and VEGF was examined in 4 colorectal carcinoma cell lines (COLO320DM, COLO201, DLD‐1, WiDr) and 149 colorectal carcinoma tissues (10 fresh specimens, 139 archival, paraffin‐embedded specimens). HIF‐1α protein levels were increased by hypoxia in 3 of 4 colorectal carcinoma cell lines (COLO201, DLD‐1, WiDr), and VEGF mRNA levels were also increased by hypoxia in the same cell lines. In 8 of 10 patients with colorectal cancer, expression of HIF‐1α and VEGF was increased in tumor tissues compared to corresponding normal mucosa. Of 139 archival specimens of colorectal carcinoma, 81 (58.3%) expressed HIF‐1α protein at a high level. HIF‐1α expression was correlated with tumor invasion, tumor stage, lymphatic invasion, venous invasion and liver metastasis. Moreover, HIF‐1α expression was correlated significantly with VEGF expression and microvessel density. Although there was a tendency for poorer prognosis in patients with high HIF‐1α‐expressing tumors, this correlation was not statistically significant. These findings suggest that HIF‐1α may play a role in angiogenesis and tumor progression via regulation of VEGF in human colorectal carcinoma.