曹雪涛院士破解炎症与癌症间的关联性

　　

生物通报道，第二军医大，浙江大学医学院的曹雪涛院士领衔的研究小组在肺癌细胞生长免疫学方面取得新的研究进展，成果登The Journal of Immunology，文章标题为：Fas Signal Promotes Lung Cancer Growth by Recruiting Myeloid-Derived Suppressor Cells via Cancer Cell-Derived PGE。该文章发表在3月15日版面上。

 

这是曹雪涛院士等人继09年3月1日在The Journal of Immunology上发表了一篇文章后的又一力作（想了解更多曹雪涛院士3月1日发表在The Journal of Immunology的文章文章请点击：http://www.ebiotrade.com/newsf/2009-3/2009317171017.htm）

 

该文章主要解析的是Fas信号系统在肺癌发病过程中的机制。目前研究认为Fasl是死亡因子，Fas则是它的受体。当一个细胞的FasL与另一个细胞的Fas结合时 ,可以导致表达Fas的细胞凋亡。Fas又称Apol，即ＣＤ95分子。人Fas基因定位于 10号染色体q2 3,基因长度约 2 5Kb，人FascDNA长度为 2 5 34bp。人FasL基因定位于 1号染色体q2 3,基因长度约 8Kb。Fas/FasL系统与自身免疫疾病、肿瘤发生、移植物耐受等均有密切关系。

 

本研究结果发现Fas信号在体外试验中没有促进3LL细胞生长的能力，但是在体内却能促进肺癌细胞生长。不过，这一促进作用在Fas系统缺失的遗传工程模型小鼠中没有出现，在Fas过度表达的3LL细胞中也没有出现，这表明，在活体中Fas信号对肺癌细胞的生长具有关键的促进作用。

 

研究结果表明，Fas信号系统通过癌细胞衍生的PGE再生骨髓源抑制性细胞，以达到促进肺癌细胞生长的作用。这些新的见解为炎症促进癌症发生，炎症促进癌症免疫逃避的理论的提出奠定了基础。

 

该文章受到国家自然基金以及国家重点基础研究项目资助。

（生物通 小茜）

生物通推荐原文检索：Fas Signal Promotes Lung Cancer Growth by Recruiting Myeloid-Derived Suppressor Cells via Cancer Cell-Derived PGE

【Abstract】

Fas/FasL system has been extensively investigated with respect to its capacity to induce cellular apoptosis. However, accumulated evidences show that Fas signaling also exhibits nonapoptotic functions, such as induction of cell proliferation and differentiation. Lung cancer is one of cancer’s refractory to the immunotherapy, however, the underlying mechanisms remain to be fully understood. In this study, we show that Fas overexpression does not affect in vitro growth of 3LL cells, but promotes lung cancer growth in vivo. However, such tumor-promoting effect is not observed in FasL-deficient (gld) mice, and also not observed in the immune competent mice once inoculation with domain-negative Fas-overexpressing 3LL cells, suggesting the critical role of Fas signal in the promotion of lung cancer growth in vivo. More accumulation of myeloid-derived suppressor cells (MDSC) and Foxp3+ regulatory T cells is found in tumors formed by inoculation with Fas-overexpressing 3LL cells, but not domain-negative Fas-overexpressing 3LL cells. Accordingly, Fas-ligated 3LL lung cancer cells can chemoattract more MDSC but not regulatory T cells in vitro. Furthermore, Fas ligation induces 3LL lung cancer cells to produce proinflammatory factor PGE2 by activating p38 pathway, and in turn, 3LL cells-derived PGE2 contribute to the Fas ligation-induced MDSC chemoattraction. Furthermore, in vivo administration of cyclooxygenase-2 inhibitor can significantly reduce MDSC accumulation in the Fas-overexpressing tumor. Therefore, our results demonstrate that Fas signal can promote lung cancer growth by recruiting MDSC via cancer cell-derived PGE2, thus providing new mechanistic explanation for the role of inflammation in cancer progression and immune escape.