Inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma

被引:43
作者
Han, Ke-Qi [1 ]
He, Xue-Qun [1 ]
Ma, Meng-Yu [1 ]
Guo, Xiao-Dong [1 ]
Zhang, Xue-Min [1 ]
Chen, Jie [1 ]
Han, Hui [1 ]
Zhang, Wei-Wei [1 ]
Zhu, Quan-Gang [2 ]
Nian, Hua [2 ]
Ma, Li-Jun [3 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Shanghai Yueyang Hosp Integrated Tradit Chinese &, Dept Oncol, Shanghai 200336, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Shanghai Yueyang Hosp Integrated Tradit Chinese &, Dept Pharm, Shanghai 200336, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Oncol, Shanghai 200336, Peoples R China
关键词
Chemokines; Gene expression profile; Hepatocellular carcinoma; PCR array; RNA interference; CXC-CHEMOKINES; PROSTATE-CANCER; METASTATIC PHENOTYPE; MALIGNANT-MELANOMA; CELL-PROLIFERATION; COLORECTAL-CANCER; TUMOR-GROWTH; PATHWAYS; SURVIVAL; INTERLEUKIN-8;
D O I
10.3748/wjg.v21.i16.4864
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
AIM: To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice. METHODS: CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed. RESULTS: Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1 beta protein. CONCLUSION: These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.
引用
收藏
页码:4864 / 4874
页数:11
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