HER2 serves as the marker for identifying radiation-resistant breast cancer stem cells
Abstract
Cancer stem cells (CSCs) are shown to be able to self-renew and be resistant to radiation therapy. Elucidation of the role of CSCs in radiation-mediated repopulation may provide critical insights for development of new approaches to resensitize resistant tumor cells. Identification of biomarkers of therapy-resistant CSCs will provide approaches to target the CSCs especially in recurrent and metastatic tumors. This thesis explores to establish a new marker for breast CSCs and offers a possible mechanism that might be responsible for their radio-resistant phenotypes. Results demonstrated that 45% of cells with the feature of CD44 +/CD24-/low are HER2 positive in the MCF7 breast cancer cells survived from therapeutic irradiation due to HER2 overexpression. The radiation-surviving cells with HER2+/CD44+/CD24 -/low feature showed a more aggressive growth with radioresistant phenotype than the HER2−/CD44+/CD24 -/low counterparts. Proteomics analysis revealed unique protein expression profiles for HER2+/CD44+/CD24-/low and HER2−/CD44+/CD24-/low fractions. Co-expression of HER2 and CD44 was increased in the recurrent tumors compared to the primary tumors from 40 patients diagnosed with breast cancers and the HER2+/CD44+/CD24-/low MCF7 cells showed an enhanced tumorigenesis in NSG mice. Thus, HER2 +/CD44+/CD24-/low shall be considered as a CSC marker for therapy-resistant breast tumors and current treatment designs should be reassessed incorporating HER2’s herein demonstrated role in radioresistant breast CSCs.
Degree
Ph.D.
Advisors
Liu, Purdue University.
Subject Area
Cellular biology|Medical imaging|Oncology
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