Breast cancer stem cells in HER2-negative breast cancer cells contribute to HER2-mediated radioresistance and molecular subtype conversion: clinical implications for serum HER2 in recurrent HER2-negative breast cancer
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Yun Gyoung Kim1,2,*, Yi Na Yoon3,5,*, Hyang Suk Choi1, Ji-Hyun Kim1, Hyesil Seol6, Jin Kyung Lee7, Min-Ki Seong1, In Chul Park3, Kwang Il Kim4, Hyun-Ah Kim1, Jae-Sung Kim3,5 and Woo Chul Noh1
1Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
2Department of Surgery, Bundang Jesaeng General Hospital, Seongnam, Korea
3Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
4RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
5Radiological and Medico-Oncological Sciences, University of Science and Technology, Seoul, Korea
6Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
7Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
*These authors contributed equally to this work
Jae-Sung Kim, email: [email protected]
Hyun-Ah Kim, email: [email protected]
Keywords: breast cancer; HER2-negative breast cancer; breast cancer stem cells; serum HER2; radioresistance
Received: September 08, 2017 Accepted: December 04, 2017 Published: December 20, 2017
Although it has been proposed that the beneficial effect of HER2-targeted therapy in HER2-negative breast cancer is associated with the molecular subtype conversion, the underlying mechanism and the clinical biomarkers are unclear. Our study showed that breast cancer stem cells (BCSCs) mediated HER2 subtype conversion and radioresistance in HER2-negative breast cancer cells and evaluated serum HER2 as a clinical biomarker for HER2 subtype conversion. We found that the CD44+/CD24–/low BCSCs from HER2-negative breast cancer MCF7 cells overexpressed HER2 and EGFR and showed the radioresistant phenotype. In addition, we showed that trastuzumab treatment sensitized the radioresistant phenotype of the CD44+/CD24–/low cells with decreased levels of HER2 and EGFR, which suggested that HER2-targeted therapy in HER2-negative breast cancer could be useful for targeting BCSCs that overexpress HER2/EGFR. Importantly, our clinical data showed that serial serum HER2 measurement synchronously reflected the disease relapse and the change in tumor burden in some patients who were initially diagnosed as HER2-negative breast cancer, which indicated that serum HER2 could be a clinical biomarker for the evaluation of HER2 subtype conversion in patients with recurrent HER2-negative breast cancer. Therefore, our data have provided in vitro and in vivo evidence for the molecular subtype conversion of HER2-negative breast cancer.
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