Hypoxia-inducible factor-lαand semaphorin4D genes involved with tumor-associated macrophage-induced metastatic behavior and clinical significance in colon cancer  

作　　者：Mu Linjun Wang Jinshen Chen Yuezhi Li Leping Guo Xiaobo Zheng Sheng Jing Changqing 

机构地区：[1]Department of Gastrointestinal Surgery, Shandong Provincial Hospitalaffiliated to Shandong University, Jinan, Shandong 250021, China

出　　处：《Chinese Medical Journal》2014年第20期3568-3575,共8页中华医学杂志（英文版）

基　　金：This study was supported in part by grants from the National Youthful Science Foundation of China （No. 81101858） and the Natural Science Foundation of Shandong Province of China （No. BS2011 SW046）. Conflict of interest： none.

摘　　要：Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha （HIF-lg） plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D （Sema4D） also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages （TAMs） can increase the expression of HIF-la and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-la and the impact of biologic behavior in colon cancer cells. Methods Immunohistochemistry was used to analyze HIF-la and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software （SPSS Inc., USA）. Differences between two groups were analyzed with Student＇s t test. Results HIF-la （58%） and Sema4D （60%） were expressed at a significantly higher level in tumors than in normal tissues （P 〈0.01, for both）. Furthermore, HIF-la and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages （P 〈0.05）, but not with age and tumor size （P 〉0.05）. Sema4D expression was correlated with that of HIF-la （r=0.567, P 〈0.01）. TAMs markedly induced HIF-la and Sema4D expression in colon cancer calls and subsequently increased their migration and invasion. Conclusions HIF-la and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-la and Sema4D.Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha （HIF-lg） plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D （Sema4D） also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages （TAMs） can increase the expression of HIF-la and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-la and the impact of biologic behavior in colon cancer cells. Methods Immunohistochemistry was used to analyze HIF-la and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software （SPSS Inc., USA）. Differences between two groups were analyzed with Student＇s t test. Results HIF-la （58%） and Sema4D （60%） were expressed at a significantly higher level in tumors than in normal tissues （P 〈0.01, for both）. Furthermore, HIF-la and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages （P 〈0.05）, but not with age and tumor size （P 〉0.05）. Sema4D expression was correlated with that of HIF-la （r=0.567, P 〈0.01）. TAMs markedly induced HIF-la and Sema4D expression in colon cancer calls and subsequently increased their migration and invasion. Conclusions HIF-la and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-la and Sema4D.

关 键 词：colon cancer hypoxia-inducible factor-1 alpha semaphorin4D tumor-associated macrophages METASTASIS 

分 类 号：Q782[生物学—分子生物学] S858.316.2[农业科学—临床兽医学]