近日，南开大学生命科学学院陈佺教授课题组在结肠癌肿瘤研究方面取得重大进展，研究成果被临床肿瘤期刊Clinical Cancer Research杂志接收。生命科学学院陈佺教授为通讯作者，博士生饶冠华为第一作者，本研究由南开大学和中国科学院动物研究所合作完成。
目前，癌症依旧是威胁人类健康和生命的重大疾病，其中结直肠癌是我国位居第四位的常见恶性肿瘤，其发病率和死亡率有逐年增高的趋势。因此，研究结肠癌并了解其癌症生物学特征已成为科学界迫切需要解决的问题。陈佺课题组的博士生饶冠华发现，在肿瘤微环境中的巨噬细胞对肿瘤的发生与发展有着重要的贡献。而在肿瘤中可能只有一小部分具有肿瘤干细胞性质的肿瘤细胞具有产生肿瘤并维持肿瘤生长的能力。因而，研究组人员把研究重点放在巨噬细胞与肿瘤干细胞之间的相互影响和交流之上，并且发现，表达CD44分子的肿瘤干细胞能够影响肿瘤微环境中的巨噬细胞并使其分泌一种细胞因子OPN（骨桥蛋白），而OPN又能反过来与肿瘤细胞表面受体分子CD44结合，进而促进肿瘤干细胞的克隆形成能力。在针对临床样品的分析结果表明，OPN与CD44分子与结肠癌患者的愈后生存期有着密切的关系。这些研究成果对于预防和治疗结肠癌提供了新的靶点和思路。
陈佺教授主要从事线粒体和细胞凋亡和线粒体自噬机制的研究，同时也开展肿瘤干细胞研究，已经在Nature Cell Biology、Nature Communications、JBC、Hepatology、Autophagy、Oncogene、Clinical Cancer Research等杂志发表研究论文50多篇。2000获得中国科学院“百人计划”，2004年自然科学基金委“杰出青年基金”获得者，2007年教育部“长江学者计划”特聘教授，2011年谈家桢生命科学创新奖获得者。现任《FEBS Letters》杂志编委，《Cell Research》和《Autophagy》杂志编委会成员。中国生物物理学会和细胞生物学会常务理事，亚洲线粒体学会秘书长。（生物谷Bioon.com）
doi:10.1158/1078-0432.CCR-12-2788
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PMID:
Reciprocal Interactions between Tumor-Associated Macrophages and CD44-Positive Cancer Cells via Osteopontin/CD44 Promote Tumorigenicity in Colorectal Cancer
Guanhua Rao1, Hongyi Wang3, Baowei Li2, Li Huang2, Danfeng Xue2, Xiaohui Wang2, Haijing Jin2, Jun Wang2, Yushan Zhu1, Youyong Lu3, Lei Du2, and Quan Chen1,2
Purpose: CD44 is of functional importance for tumor initiation and progression in colorectal cancer, but how this molecule benefits cancer cells from the tumor microenvironment, especially tumor-associated macrophages (TAM), remains poorly defined. Experimental Design: In vivo tumorigenic assays were conducted to assess the role of murine TAMs in the tumorigenesis of human colorectal cancer cells. Both in vitro and in vivo osteopontin (OPN) expression levels in TAMs were examined by immunohistochemistry, quantitative PCR, and Western blotting. Soft agar colony formation assays were used to estimate the clonogenicity of colorectal cancer cells that had received different treatments. The relationships between the expression levels of OPN, CD44v6, and CD68 and clinical prognosis were evaluated by tissue microarray analysis. Results: We found that macrophages, when coinjected or cocultured with CD44-positive colorectal cancer cells, were able to produce higher levels of OPN, which in turn facilitated the tumorigenicity and clonogenicity of the colorectal cancer cells. The knockdown of CD44 or treatment with blocking antibodies to CD44 attenuated OPN secretion. OPN, through binding to its receptor CD44, activated c-jun-NH2-kinase signaling and promoted the clonogenicity of colorectal cancer cells. Moreover, tissue microarray data have shown that OPN expression, in combination with CD44v6, has a negative correlation with colorectal cancer patient survival. Conclusions: These results suggest that the OPN–CD44 interaction is important for colorectal cancer progression and could serve as a potential therapeutic target for the treatment of colorectal cancer. Clin Cancer Res; 19(4); 785–97. ©2012 AACR.
