傅永强　郭方明　陈浩浩

[摘要] 目的 探讨空芯针穿刺活检（core needle biopsy，CNB）对乳腺癌远处转移的影响及其可能机制。 方法 30只BALB/c小鼠采用乳腺癌4T1细胞乳腺脂肪垫接种， 分成活检与非活检两组，活检组应用CNB建立活检相关肺转移模型，采用流式细胞术、qPCR及形态学等检测技术从肿瘤组织局部和整体水平评价其生物学行为。 结果 成功建立稳定而可靠的乳腺癌肺转移模型，活检组小鼠肺转移结节数显著高于非活检组（P<0.05）；与非活检组相比，活检组小鼠TGF-β1、SOX-4及EZH2的mRNA表达上调（P<0.05），流式细胞术检测的NK细胞增加，但差异无统计学意义（P>0.05）。 结论 CNB可通过TGF-β信号通路介导的上皮-间质转化（epithelial-mesenchymal transition，EMT）等机制促进乳腺癌的肺转移。

[关键词] 乳腺癌；肺转移；活检；上皮间质转化；小鼠

[中图分类号] R737.9 [文献标识码] A [文章编号] 1673-9701（2018）23-0028-05

Experimental sudy on the TGF-β signaling pathway in promoting mice breast cancer biopsy-related lung metastasis

FU Yongqiang1 GUO Fangming1 CHEN Haohao1 FU Xiaoyan1 HE Guochan1 ZHANG Hui2 FANG Yuanshu2 YING Xiaoqian1 ZHANG Ning1 DING Mingxing1

1.Jinhua Polytechnic Medical School， Jinhua 321007， China； 2.Jinhua Institute of Food and Drug Test Center in Zhejiang Province， Jinhua 321007， China

[Abstract] Objective To investigate the effect of core needle biopsy（CNB） on distant metastasis of breast cancer and its possible mechanism. Methods 30 BALB/c mice were inoculated with mammary fat pad of breast cancer 4T1 cells. They were divided into biopsy group and non-biopsy group. The biopsy group was given CNB to establish a biopsy-related lung metastasis model. Flow cytometry， qPCR， and morphological techniques were used to evaluate the biological behavior by the local and global levels of tumor tissues. Results After successfully establishing a stable and reliable breast cancer lung metastasis model， the number of lung metastatic nodules in the biopsy group was significantly higher than that in the non-biopsy group（P<0.05）； Compared with non-biopsy group， mRNA expression of TGF-β1， SOX-4 and EZH2 in the biopsy group was up-regulated（P<0.05）. NK cells detected by flow cytometry were increased， but the difference was not statistically significant（P>0.05）. Conclusion CNB can promote lung metastasis of breast cancer through TGF-β signaling pathway-mediated epithelial-mesenchymal transition （EMT） and other mechanisms.

[Key words] Breast cancer； Pulmonary metastasis； Biopsy； Epithelial-mesenchymal transition （EMT）； Mice

乳腺癌的發病率和致死率均高居女性恶性肿瘤首位，转移和侵袭是其致死的主要原因，故筛查和早期检测对于改善患者预后及生活质量极为关键[1，2]。其中空芯针穿刺活检（core needle biopsy，CNB）是目前主要的活检方法，但其对临床患者结局的影响和潜在风险尚有争议，CNB可增加乳腺癌患者肿瘤细胞的针道种植及穿刺部位皮肤转移的机会，并有促进肿瘤局部复发及远处转移的风险[3，4]。其机制可能涉及一系列肿瘤细胞与细胞外基质（extracellular matrix，ECM）的相互作用过程，而TGF-β信号通路通过其下游的多种转录因子介导的上皮-间质转化（epithelial-mesenchymal transition，EMT）在乳腺癌发生及转移中有重要作用[5]。新近发现，SOX转录因子中SOX-4参与调控TGF-β1诱导的人乳腺上皮细胞EMT过程，通过EZH2基因表观遗传修饰发挥作用，可作为临床三阴性乳腺癌的潜在生物标志[6，7]。本文应用小……