非可控性炎症的恶性转化

The Malignant Transformation of Nonresolving Inflammation

炎症和肿瘤之间存在内源性及外源性两条通路,它们在非可控性炎症恶性转化的过程中起重要作用。机体内有多种消炎机制的存在,当炎性因素如组织损伤或者感染消除后,炎症很快结束;如果存在持续的或低强度刺激时,炎症将不可控制。在非可控性炎症状态下,炎症介质尤其是活性氧氮介质引起原癌基因活化和抑癌基因灭活,启动肿瘤;NF-κB和STAT3通路活化后与促炎细胞因子间存在正反馈循环,共同促进肿瘤的发展,新生血管的形成,上皮间质转化(EMT)的发生;炎症细胞释放的金属蛋白酶(MMP)有利于肿瘤的侵袭和转移。此外,肿瘤微环境中的炎症细胞如肿瘤相关性巨噬细胞(TAMs)、骨髓来源抑制细胞(MD-SC),炎症介质如肿瘤坏死因子(TNF)等影响肿瘤发生、发展及侵袭转移。研究非可控性炎症恶性转化的机制可为肿瘤的预防和治愈提供新的思路。

Inflammation and tumor exist intrinsic and extrinsic pathways,which play an important role in the process of malignant transformation of nonresolving inflammation.Usually,as the presence of a variety of anti-inflammatory mechanism in the body,inflammation would disappear rapidly when inflammatory factors such as tissue damage or infection were eliminated;if there is sustained or low-intensity stimulation,inflammation will become uncontrollable.In the state of uncontrolled inflammation,inflammatory mediators,especially reactive oxygen and nitrogen species will lead to activation of oncogene and inactivation of tumor suppressor gene;positive feedback loops will exist between proinflammatory cytokines and the activation of NF-κB and STAT3 pathways,respectively,which can promote the development of tumors,angiogenesis,epithelial-mesenchymal transition（EMT）;Matrix metalloproteinase（MMP）released from inflammation cells will contributes to tumor invasion and metastasis.In addition,the inflammatory cells in the tumor microenvironment,such as tumor-associated macrophages（TAMs）,myeloid-derived suppressor cells（MDSC）,inflammatory mediators like tumor necrosis factor（TNF） affect tumor occurrence,development and evolution,invasion and metastasis.Study of malignant transformation mechanism of nonresolving inflammation can provide new ideas for the prevention and therapy of the cancer.