Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells.

Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells.
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DOI:
10.1039/c4mb00710g
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发表时间:
2015-03
影响因子:
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通讯作者:
Y. Mao;Yuzi Zhang;Q. Qu;Meizhong Zhao;Ying Lou;Junjun Liu;O. Huang;Xiao-song Chen;Jiayi Wu;K. Shen
Y. Mao;Yuzi Zhang;Q. Qu;Meizhong Zhao;Ying Lou;Junjun Liu;O. Huang;Xiao-song Chen;Jiayi Wu;K. Shen
中科院分区:
生物3区
文献类型:
--
作者:
Y. Mao;Yuzi Zhang;Q. Qu;Meizhong Zhao;Ying Lou;Junjun Liu;O. Huang;Xiao-song Chen;Jiayi Wu;K. Shen

文献摘要

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癌症相关成纤维细胞是否以及如何诱导HER 2+乳腺癌中的曲妥珠单抗耐药仍然是难以捉摸的。我们分析了与CAF条件培养基(CM)共培养的HER 2阳性乳腺癌细胞中曲妥珠单抗治疗前后癌症干细胞的百分比和多途径状态。结果表明,CAF通过扩增肿瘤干细胞并激活多种途径(如NF-κB、JAK/STAT 3和PI 3 K/AKT)诱导曲妥珠单抗耐药;抗IL 6抗体或多途径抑制剂与曲妥珠单抗联合治疗HER 2阳性乳腺癌可能是逆转曲妥珠单抗耐药的新策略。
Whether and how cancer-associated fibroblasts induce trastuzumab resistance in HER2+ breast cancer is still elusive. We analyzed the percentage of cancer stem cells and multiple pathway status before and after trastuzumab treatment in HER2 positive breast cancer cells co-cultured with conditional medium (CM) from CAFs. The results suggest that CAFs induce trastuzumab resistance by expanding cancer stem cells and activating multiple pathways, such as NF-κB, JAK/STAT3 and PI3K/AKT; combination of an anti-IL6 antibody, or multiple pathway inhibitors with trastuzumab in HER2 positive breast cancer maybe a novel strategy to reverse trastuzumab resistance.