近日,，南開(kāi)大學(xué)生命科學(xué)學(xué)院陳佺教授課題組在結(jié)腸癌腫瘤研究方面取得重大進(jìn)展，研究成果被臨床腫瘤期刊Clinical Cancer Research雜志接收,。生命科學(xué)學(xué)院陳佺教授為通訊作者,，博士生饒冠華為第一作者，本研究由南開(kāi)大學(xué)和中國(guó)科學(xué)院動(dòng)物研究所合作完成,。
目前,，癌癥依舊是威脅人類健康和生命的重大疾病，其中結(jié)直腸癌是我國(guó)位居第四位的常見(jiàn)惡性腫瘤,，其發(fā)病率和死亡率有逐年增高的趨勢(shì),。因此，研究結(jié)腸癌并了解其癌癥生物學(xué)特征已成為科學(xué)界迫切需要解決的問(wèn)題,。陳佺課題組的博士生饒冠華發(fā)現(xiàn),，在腫瘤微環(huán)境中的巨噬細(xì)胞對(duì)腫瘤的發(fā)生與發(fā)展有著重要的貢獻(xiàn)。而在腫瘤中可能只有一小部分具有腫瘤干細(xì)胞性質(zhì)的腫瘤細(xì)胞具有產(chǎn)生腫瘤并維持腫瘤生長(zhǎng)的能力,。因而,，研究組人員把研究重點(diǎn)放在巨噬細(xì)胞與腫瘤干細(xì)胞之間的相互影響和交流之上,，并且發(fā)現(xiàn),，表達(dá)CD44分子的腫瘤干細(xì)胞能夠影響腫瘤微環(huán)境中的巨噬細(xì)胞并使其分泌一種細(xì)胞因子OPN（骨橋蛋白），而OPN又能反過(guò)來(lái)與腫瘤細(xì)胞表面受體分子CD44結(jié)合,，進(jìn)而促進(jìn)腫瘤干細(xì)胞的克隆形成能力,。在針對(duì)臨床樣品的分析結(jié)果表明，OPN與CD44分子與結(jié)腸癌患者的愈后生存期有著密切的關(guān)系,。這些研究成果對(duì)于預(yù)防和治療結(jié)腸癌提供了新的靶點(diǎn)和思路,。
陳佺教授主要從事線粒體和細(xì)胞凋亡和線粒體自噬機(jī)制的研究，同時(shí)也開(kāi)展腫瘤干細(xì)胞研究,，已經(jīng)在Nature Cell Biology,、Nature Communications、JBC,、Hepatology,、Autophagy、Oncogene,、Clinical Cancer Research等雜志發(fā)表研究論文50多篇,。2000獲得中國(guó)科學(xué)院“百人計(jì)劃”，2004年自然科學(xué)基金委“杰出青年基金”獲得者,，2007年教育部“長(zhǎng)江學(xué)者計(jì)劃”特聘教授,，2011年談家楨生命科學(xué)創(chuàng)新獎(jiǎng)獲得者?，F(xiàn)任《FEBS Letters》雜志編委，《Cell Research》和《Autophagy》雜志編委會(huì)成員,。中國(guó)生物物理學(xué)會(huì)和細(xì)胞生物學(xué)會(huì)常務(wù)理事,，亞洲線粒體學(xué)會(huì)秘書(shū)長(zhǎng)。（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.
