Mu Linjun, Wang Jinshen, Chen Yuezhi, Li Leping, Guo Xiaobo, Zheng Sheng, Jing Changqing
Department of Gastrointestinal Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.
Department of Gastrointestinal Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China. Email:
Chin Med J (Engl). 2014;127(20):3568-75.
Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) 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-1α 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-1α and the impact of biologic behavior in colon cancer cells.
Immunohistochemistry was used to analyze HIF-1α 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.
HIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P < 0.01, for both). Furthermore, HIF-1α 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-1α (r = 0.567, P < 0.01). TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion.
HIF-1α 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-1α and Sema4D.
缺氧促进肿瘤血管生成，而缺氧诱导因子-1α（HIF-1α）在此过程中起关键作用。最近发现的促血管生成因子，信号素4D（Sema4D）也促进血管生成并增强某些肿瘤的侵袭性增殖。此外，肿瘤相关巨噬细胞（TAM）可增加癌细胞中HIF-1α和Sema4D的表达，从而影响肿瘤的生长和进展。本研究的目的是评估TAM对Sema4D和HIF-1α表达的影响以及对结肠癌细胞生物学行为的影响。
采用免疫组织化学法分析86例根治性切除的结肠癌样本和52例正常结肠组织样本中HIF-1α和Sema4D的表达。分析它们的表达与临床病理因素之间的关系。此外，还使用体外共培养系统研究巨噬细胞与肿瘤细胞的相互作用，如转移、血管生成。使用SPSS 17.0软件（美国SPSS公司）进行统计分析。两组间差异采用Student's t检验分析。
HIF-1α（58%）和Sema4D（60%）在肿瘤中的表达水平显著高于正常组织（两者P均<0.01）。此外，HIF-1α和Sema4D的表达与淋巴转移、特定组织学类型和TNM分期显著相关（P<0.05），但与年龄和肿瘤大小无关（P>0.05）。Sema4D的表达与HIF-1α的表达相关（r=0.567，P<0.01）。TAM显著诱导结肠癌细胞中HIF-1α和Sema4D的表达，并随后增加其迁移和侵袭能力。
HIF-1α和Sema4D的表达与结肠癌的淋巴转移、特定组织学类型和TNM分期密切相关。此外，TAM可能通过上调HIF-1α和Sema4D促进结肠癌细胞的迁移和侵袭以及内皮管形成。
