Effect Of Cancer-Associated Fibroblasts On Trastuzumab Resistance By Activating Multiple Pathways In Her2-Positive Breast Cancer

e11587 Background: HER2 positive breast cancer accounts for about 25% of this malignancy, which was characterized by an aggressive clinical course. Trastuzumab, an anti-HER2 targeted agent, has improved the prognosis of this kind of patients. However, almost 50% of them will develop trastuzumab resistance within 1 to 2 years treatment. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, have related to drug resistance, but whether and how they mediate trastuzumab resistance in HER2 positive breast cancer remain unclear. Methods: CAFs and normal fibroblasts (NFs) were isolated from fresh HER2+ breast samples obtained from Ruijin hospital. Conditional medium (CM) were collected from cultured CAFs and NFs. Different secreted proteins were analyzed by RayBio human cytokine antibody Array. Cell proliferation was determined by XTT assay and colony formation assay. Gene expression was analyzed by real-time PCR. Protein expression was determined by western-blotting. Gene transcrip...