肿瘤相关巨噬细胞(TAMs)促进Ⅰ型子宫内膜癌细胞增殖和侵袭

Tumor-associated macrophages(TAMs)promote the proliferation and invasion of type I endometrial carcinoma

目的研究肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)对Ⅰ型子宫内膜癌增殖转移的影响及其分子生物学机制。方法免疫组化方法分析正常及各类型子宫内膜增生性病变(增殖期、分泌期、单纯增生、复杂增生、不典型和I型子宫内膜癌)组织中巨噬细胞浸润情况。CCK-8法和Transwell法分别检测单核巨噬细胞系THP-1(构建为M2型TAMs后)对Ⅰ型子宫内膜癌细胞系RL95-2增殖和侵袭能力的影响,Transwell法检测RL95-2对THP-1的招募作用。Western blot技术检测THP-1对RL95-2的CyclinD1和MMP-2表达影响。结果免疫组化结果显示,TAMs浸润数目与子宫内膜增生性病变进展程度呈正相关。RL95-2可招募THP-1,招募的THP-1促进RL95-2的增殖和侵袭,MMP-2和CyclinD1表达随THP-1作用而呈时间依赖性上调(P<0.05)。结论巨噬细胞浸润增加造成的肿瘤周围炎症微环境可能是Ⅰ型子宫内膜癌发展的机制之一。

Objective To explore the influence of tumor-associated macrophages （TAMs） on the proliferation and invasion of type Ⅰ endometrial carcinoma and its mechanisms.Methods Immunohistochemistry was used to investigate the infiltration of macrophages in normal and hyperplastic endometrial lesions （proliferative phase,secretory phase normal endometrium,simple,complex and atypical hyperplasia,type Ⅰ endometrail carcinoma）.In in vitro study,the influence of macrophage cell line THP-1 （induced to M2 type macrophages） on the proliferation and invasion of endometrial cancer cell line RL95-2 was detected by cck-8 and transwell technologies respectively.Transwell was also used to evaluate the recruitind ability of RL95-2 on THP-1 cells.Furthermore,the effects of THP-1 on the expressions of CyclinD1 and MMP-2 in RL95-2 were tested by Western blot.Results The number of macrophages at lesion site was positively correlated with endometrial hyperplasia.THP-1 recruited by RL95-2 could promote the proliferation and invasion of RL95-2,with the expression of CyclinD1 and MMP 2 up-regulated in a time dependent manner.Conclusions Tumor inflammatory microenvironment resulted from macrophages migration might be one of the mechanisms promoting development of type Ⅰ endometrial carcinoma.