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PLoS ONE:结肠癌发生致病因素研究获进展

来源:《PLoS综合》 2011-05-20 16:14

近日来自上海交通大学医学院的研究人员在结肠癌领域取得突破性成果,在小鼠中CCL20/CCR6轴可作为关键性致病因素推动结肠癌的发生发展。相关研究成果发表在国际著名的《公共科学图书馆—综合》(PLoS ONE)杂志上。

领导这一研究的是上海交大的特聘教授王宏林博士,其2006年获得德国乌尔姆大学博士学位。

结肠癌是一种预后极差的消化系统恶性肿瘤。近年来,结肠癌的发病率逐年上升,且恶性程度更高,预后更差。在这篇文章中,研究人员证实肿瘤相关巨噬细胞可通过分泌CCL20招募CCR6阳性调节性T细胞,促进小鼠结肠癌的发生发展。课题组以 CCL20 / CCR6轴为控制靶点,通过激活或拮抗趋化因子CCL20受体CCR6的信号传导通路控制 CCL20 / CCR6系统的功能。随后,通过选择性消除巨噬细胞的结肠癌小鼠模型,研究人员发现,选择性消除巨噬细胞后,结肠癌小鼠肿瘤微环境中CCL20的分泌减少,趋化CCR6阳性调节性T细胞的能力下降。

该研究成果揭示了在结肠癌的发生发展过程中CCL20/ CCR6轴可作为关键致病因素推动病程进展,对寻找和明确结肠癌的药物干预靶点具有较高学术价值。(生物谷Bioon.com)

生物谷推荐原文出处:

PLoS ONE   DOI:10.1371/journal.pone.0019495

Tumor-Associated Macrophages Recruit CCR6+ Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice

Jinlin Liu,Ning Zhang,Qun Li,Weiwei Zhang,Fang Ke,Qibin Leng,Hong Wang,Jinfei Chen,Honglin Wang,

Background Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. Methodology/Principal Findings CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3GFP+) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. Conclusions/Significance TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model.

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