title: Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells.
abstract: 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.
authors: Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2 Road, Shanghai, 200025, China. kwshen@medmail.com.cn.
authors: Yan
authors: Y
authors: Mao
authors: Yuzi
authors: Y
authors: Zhang
authors: Qing
authors: Q
authors: Qu
authors: Meizhong
authors: M
authors: Zhao
authors: Ying
authors: Y
authors: Lou
authors: Junjun
authors: J
authors: Liu
authors: Ou
authors: O
authors: huang
authors: Xiaosong
authors: X
authors: Chen
authors: Jiayi
authors: J
authors: Wu
authors: Kunwei
authors: K
authors: Shen
mesh_terms: D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D014411:Neoplastic Stem Cells; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D051242:Caveolin 1; D015850:Interleukin-6; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D000093242:Interleukin-6 Inhibitors; C541116:ACTA2 protein, human; C495540:CAV1 protein, human; C508600:IL6 protein, human