肿瘤相关巨噬细胞促进宫颈癌侵袭转移的机制研究

目的研究肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)对宫颈癌侵袭转移的影响及分子机制。方法免疫组织化学法检测宫颈病变组织TAMs的浸润情况。对人单核巨噬细胞系THP1进行体外诱导分化,使其转化为M2型TAMs。取TAMs上清液刺激宫颈癌细胞SiHa和C33a。划痕法、Transwell法分别检测TAMs对宫颈癌细胞系迁移和侵袭能力的影响。Western blot检测刺激后宫颈癌细胞上皮间质转化进程及MMP-9的表达。结果 TAMs浸润数目与宫颈病变进展呈正相关。TAMs上清液刺激后,SiHa和C33a细胞出现间质样改变,而且迁移和侵袭能力显著增强(均P<0.5)。TAMs可下调E-Cadherin的表达,上调N-Cadherin、Vimentin及MMP-9的表达。结论 TAMs浸润与宫颈上皮恶性转化和进展密切相关,TAMs可能通过上调MMP-9的表达促进宫颈癌细胞侵袭转移。

Tumor-associated Macrophages Promote Invasion and Metastasis of Cervical Cancer

Objective To investigate the effect and mechanism of tumor-associated macrophages (TAMs) on the invasion and metastasis of cervical cancer. Methods Immunohistochemical method was used to detect the infiltration of TAMs in cervical lesions. The human mononuclear THP1 cell line was induced to transform into M2 type TAMs in vitro. TAMs were used to stimulate cervical cancer cells (SiHa and C33a). Scratch and Transwell assays were used to detect the effect of TAMs on the migration and invasion of cervical cancer cell lines. Western blot was used to detect the epithelial-mesenchymal transition and the expression of MMP-9 in cervical cancer cells. Results The number of TAM infiltration was positively correlated with the progression of cervical lesions. After stimulated by TAMs-CM, SiHa and C33a cells appeared interstitial-like changes, and the migration and invasion abilities were significantly enhanced (both P<0.5). TAMs could down-regulate the expression of E-Cadherin, and up-regulate the expression of N-Cadherin, Vimentin and MMP-9. Conclusion The invasion of TAMs is closely related to the malignant transformation and progression of cervical epithelium. TAMs may promote the invasion and metastasis of cervical cancer cells by up-regulating the expression of MMP-9.