Expression of hypoxia-inducible factor-lα is associated with tumor vascularization in human colorectal carcinoma

被引:140
作者
Kuwai, T
Kitadai, Y
Tanaka, S
Onogawa, S
Matsutani, N
Kaio, E
Ito, M
Chayama, K
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Med & Mol Sci, Minami Ku, Hiroshima 7348551, Japan
[2] Hiroshima Univ Hosp, Dept Endoscopy, Hiroshima, Japan
关键词
HIF-1; alpha; vascular endothelial growth factor; angiogenesis; colorectal cancer;
D O I
10.1002/ijc.11068
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
HIF-1 is reported to transactivate expression of VEGF, which is an important angiogenic factor. To determine whether HIF-1alpha plays a role in angiogenesis through its regulation of VEGF, we examined expression of HIF-1alpha and its relation to clinicopathologic features, VEGF expression and prognosis of patients with colorectal carcinoma. Expression of HIF-1alpha 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-em bedded specimens). HIF-1alpha protein levels were increased by hypoxia in 3 of 4 colorectal carcinoma cell lines (COLO201, DLD-I, 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-1alpha and VEGF was increased in tumor tissues compared to corresponding normal mucosa. Of 139 archival specimens of colorectal carcinoma, 81 (58.3%) expressed HIF-1alpha protein at a high level. HIF-1alpha expression was correlated with tumor invasion, tumor stage, lymphatic invasion, venous invasion and liver metastasis. Moreover, HIF-1alpha expression was correlated significantly with VEGF expression and microvessel density. Although there was a tendency for poorer prognosis in patients with high HIF-1alpha-expressing tumors, this correlation was not statistically significant. These findings suggest that HIF-Ialpha may play a role in angiogenesis and tumor progression via regulation of VEGF in human colorectal carcinoma. (C) 2003 Wiley-Liss, Inc.
引用
收藏
页码:176 / 181
页数:6
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