Angiogenin expression in human colorectal cancer: The role of focal macrophage infiltration

Tumor angiogenesis is essential for tumor growth and tumor metastasis, and it depends on angiogenic factors produced by tumor cells and/or infiltratin g cells in tumor tissue. In this study, we evaluated the clinical significa nce of the expression of angiogenin, which is a potent angiogenic protein, and the relationship between its mRNA expression and focal macrophage infil tration in colorectal cancer. Furthermore, we investigated the induction of angiogenin mRNA expression by proinflammatory cytokines mainly produced by inflammatory cells in tumor tissues. When we examined the relationship bet ween the mRNA expression of angiogenin, by semiquantitative reverse transcr iption-PCR, and clinicopathological features in 65 patients with colorectal cancer, there was a significant difference in the vascular involvement, ly mph node metastasis, liver metastasis, and advanced stage in patients with high-expression of angiogenin compared with low expression (P < 0.05). With regard to prognosis, the survival time for subjects in the high angiogenin mRNA group (tumor:normal ratio >1.9) was significantly worse (P < 0.05). W hen we examined the localization of angiogenin in colorectal cancer, immuno histochemical analysis in 65 patients with colorectal cancer revealed that angiogenin was predominantly expressed in cancer cells compared with stroma l cells or normal tissues. The intensity of staining of angiogenin was sign ificantly correlated with microvessel counts and focal macrophage infiltrat ion counts (P < 0.05). In an in vitro study, interleukin-lp and tumor necro sis factor-or induced angiogenin mRNA expression in colon cancer cells in a dose- and time-dependent manner, and these cytokines significantly up-regu lated the expression of angiogenin mRNA, especially in colon cancer cells r ather than in other cells in the stroma of tumor tissues (fibroblasts, tumo r infiltrating lymphocytes, macrophages). These results suggest that tumor angiogenesis in colorectal cancer may be advanced, at least in part, by ang iogenin induced by proinflammatory cytokines derived from infiltrating macr ophages.