title: CD44/cellular prion protein interact in multidrug resistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy in breast cancer patients.
abstract: Multidrug resistance (MDR) is one of the most important factors leading to chemotherapeutic failure in patients with breast cancer. The invasive/metastatic ability of MDR cells is strengthened compared with their parental cells. However, the mechanisms underlying MDR have not been fully elucidated. We found that CD44 and the cellular prion protein (PrPc) were both overexpressed in MDR cells (MCF7/Adr and H69AR). Subsequently, we chose the human breast cancer cell line MCF7/Adr, which is resistant to adriamycin, for further research. We discovered that PrPc physically and functionally interacted with CD44. The knockdown of CD44 or PrPc by siRNA in MCF7/Adr cells inhibited cell migration, invasion and proliferation in vitro. However, when the MCF7/Adr cells transfected with CD44 siRNA were incubated with 10 times the peak plasma concentration (PPC) of taxol, their invasive ability was again enhanced. In the breast-carcinoma tissue samples, a significant correlation between the CD44 expression and the PrPc expression was observed in the postneoadjuvant-chemotherapy (NAC) cases. Moreover, in Group 2, which was unresponsive to NAC, the CD44 and PrPc expression levels were significantly increased in the post-NAC cases compared with the pre-NAC cases using the paired-samples t-test. These data indicate that the CD44/PrPc interaction enhances the malignancy of breast cancer cells and affects the responses to neoadjuvant chemotherapy in breast cancer patients. Therefore, blocking the CD44/PrPc interaction may improve outcomes in chemorefractory breast cancer patients.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Lili
authors.initials: L
authors.lastname: Tao
authors.forename: Jiawen
authors.initials: J
authors.lastname: Xu
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.forename: Yiting
authors.initials: Y
authors.lastname: Jin
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Zude
authors.initials: Z
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018276:Carcinoma, Medullary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D018621:PrPC Proteins; D012333:RNA, Messenger
keywords: breast cancer; chemotherapy; invasion/metastasis; proliferation