TGF—β信號通路促進(jìn)小鼠乳腺癌活檢相關(guān)性肺轉(zhuǎn)移的實驗研究

傅永強(qiáng)　郭方明　陳浩浩

[摘要] 目的 探討空芯針穿刺活檢（core needle biopsy，CNB）對乳腺癌遠(yuǎn)處轉(zhuǎn)移的影響及其可能機(jī)制。 方法 30只BALB/c小鼠采用乳腺癌4T1細(xì)胞乳腺脂肪墊接種， 分成活檢與非活檢兩組，活檢組應(yīng)用CNB建立活檢相關(guān)肺轉(zhuǎn)移模型，采用流式細(xì)胞術(shù)、qPCR及形態(tài)學(xué)等檢測技術(shù)從腫瘤組織局部和整體水平評價其生物學(xué)行為。 結(jié)果 成功建立穩(wěn)定而可靠的乳腺癌肺轉(zhuǎn)移模型，活檢組小鼠肺轉(zhuǎn)移結(jié)節(jié)數(shù)顯著高于非活檢組（P<0.05）；與非活檢組相比，活檢組小鼠TGF-β1、SOX-4及EZH2的mRNA表達(dá)上調(diào)（P<0.05），流式細(xì)胞術(shù)檢測的NK細(xì)胞增加，但差異無統(tǒng)計學(xué)意義（P>0.05）。 結(jié)論 CNB可通過TGF-β信號通路介導(dǎo)的上皮-間質(zhì)轉(zhuǎn)化（epithelial-mesenchymal transition，EMT）等機(jī)制促進(jìn)乳腺癌的肺轉(zhuǎn)移。

[關(guān)鍵詞] 乳腺癌；肺轉(zhuǎn)移；活檢；上皮間質(zhì)轉(zhuǎn)化；小鼠

[中圖分類號] R737.9 [文獻(xiàn)標(biāo)識碼] A [文章編號] 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(fā)病率和致死率均高居女性惡性腫瘤首位，轉(zhuǎn)移和侵襲是其致死的主要原因，故篩查和早期檢測對于改善患者預(yù)后及生活質(zhì)量極為關(guān)鍵[1，2]。其中空芯針穿刺活檢（core needle biopsy，CNB）是目前主要的活檢方法，但其對臨床患者結(jié)局的影響和潛在風(fēng)險尚有爭議，CNB可增加乳腺癌患者腫瘤細(xì)胞的針道種植及穿刺部位皮膚轉(zhuǎn)移的機(jī)會，并有促進(jìn)腫瘤局部復(fù)發(fā)及遠(yuǎn)處轉(zhuǎn)移的風(fēng)險[3，4]。其機(jī)制可能涉及一系列腫瘤細(xì)胞與細(xì)胞外基質(zhì)（extracellular matrix，ECM）的相互作用過程，而TGF-β信號通路通過其下游的多種轉(zhuǎn)錄因子介導(dǎo)的上皮-間質(zhì)轉(zhuǎn)化（epithelial-mesenchymal transition，EMT）在乳腺癌發(fā)生及轉(zhuǎn)移中有重要作用[5]。新近發(fā)現(xiàn)，SOX轉(zhuǎn)錄因子中SOX-4參與調(diào)控TGF-β1誘導(dǎo)的人乳腺上皮細(xì)胞EMT過程，通過EZH2基因表觀遺傳修飾發(fā)揮作用，可作為臨床三陰性乳腺癌的潛在生物標(biāo)志[6，7]。本文應(yīng)用小……