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CD44/Cellular prion protein interact in multidrug resistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy in breast cancer patients
Author(s) -
Cheng Yuanyuan,
Tao Lili,
Xu Jiawen,
Li Qingquan,
Yu Juan,
Jin Yiting,
Chen Qi,
Xu Zude,
Zou Qiang,
Liu Xiuping
Publication year - 2014
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22021
Subject(s) - cd44 , biology , cancer research , multiple drug resistance , breast cancer , chemotherapy , gene knockdown , cancer , malignancy , cancer cell , medicine , in vitro , oncology , drug resistance , cell culture , biochemistry , genetics , microbiology and biotechnology
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. © 2013 Wiley Periodicals, Inc.