癌相关成纤维细胞在乳腺癌侵袭转移及耐药中的作用研究进展
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吴德全, Email: dqwu56@163.com

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Research progress of actions of cancer-associated fibroblasts in invasion, metastasis and drug resistance in breast cancer
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    摘要:

    癌相关成纤维细胞(CAF)是肿瘤微环境中主要的基质细胞。CAF可在血小板源性生生长因子、成纤维细胞生长因子、白介素6及肝细胞生长因子等多种分泌因子作用下由正常成纤维细胞转化形成,也可由间充质干细胞、脂肪细胞等多种细胞可通过上皮间质转化(EMT)过程形成,还有部分由癌症干细胞转化而来。近来有研究显示,乳腺癌中的CAF可通过分泌多种细胞因子及外泌体、参与EMT及细胞外基质重塑,进而促进乳腺癌细胞侵袭转移,也可在肿瘤缺氧微环境下通过激活相关信号通路促进乳腺癌细胞生长和侵袭。此外,CAF通过增加了乳腺癌细胞的凋亡阈值、作为抗肿瘤药物的物理屏障、分泌的谷氨酰胺增加乳腺癌细胞的存活率、激活生长因子相关的信号通路或增加线粒体功能产生抗凋亡作用等多种途径介导乳腺癌化疗耐药、内分泌治疗耐药及多药耐药。笔者总结CAF的重要来源及其在乳腺癌侵袭转移与治疗耐药中的研究进展。

    Abstract:

    Cancer-associated fibroblasts (CAFs) are one of the major stroma cells in tumor microenvironment. CAFs are usually derived from the normal fibroblasts by the actions of various platelet derived growth factor and fibroblast growth factor, interleukin 6 and hepatocyte growth factor, or from the mesenchymal stem cells, fat cells and other cells during the process of epithelial mesenchymal transformation (EMT), and some CAFs are transformed from cancer stem cells. Recent studies have demonstrated that the CAFs in breast cancer can promote the invasion and metastasis of breast cancer cells through secreting a variety of cytokines and exosomes, and participating in EMT and extracellular matrix remodeling, and also promote the growth and invasion of the breast cancer cells under the hypoxic tumor microenvironment through activating the relevant signaling pathways. Moreover, CAFs mediate the chemotherapy resistance, endocrine therapy resistance and multi-drug resistance in breast cancer through various ways such as elevating the apoptosis threshold, serving as a physical barrier against anti-tumor drugs, secreting glutamine for increasing the survival rate of breast cancer cells, activating the growth factor-associated signaling pathways or increasing mitochondrial function to produce anti-apoptotic effects. Here, the authors mainly address the research progress in sources of CAFs and its role in invasion/metastasis and treatment resistance of breast cancer.

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孙雪梅, 樊文哲, 吴德全.癌相关成纤维细胞在乳腺癌侵袭转移及耐药中的作用研究进展[J].中国普通外科杂志,2020,29(5):618-624.
DOI:10.7659/j. issn.1005-6947.2020.05.014

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  • 收稿日期:2019-10-10
  • 最后修改日期:2020-04-21
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  • 在线发布日期: 2020-05-25