Abstract
Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify patients for adjuvant therapies. Recently, a role of the receptor of hyaluronan-mediated motility (RHAMM) has been suggested for tumor progression. Our aim was (i) to investigate the prognostic value of RHAMM in breast cancer and (ii) to unravel its potential function in the radiosusceptibility of breast cancer cells. We demonstrate that RHAMM mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival. Radiosusceptibility in vitro was evaluated by sub-G1 analysis (apoptosis) and determination of the proliferation rate. The potential role of RHAMM was addressed by short interfering RNAs against RHAMM and its splice variants. High expression of RHAMMv1/v2 in p53 wild type cells (MCF-7) induced cellular apoptosis in response to ionizing radiation. In comparison, in p53 mutated cells (MDA-MB-231) RHAMMv1/v2 was expressed sparsely resulting in resistance towards irradiation induced apoptosis. Proliferation capacity was not altered by ionizing radiation in both cell lines. Importantly, pharmacological inhibition of the major ligand of RHAMM, hyaluronan, sensitized both cell lines towards radiation induced cell death. Based on the present data, we conclude that the detection of RHAMM splice variants in correlation with the p53 mutation status could help to predict the susceptibility of breast cancer cells to radiotherapy. Additionally, our studies raise the possibility that the response to radiotherapy in selected cohorts may be improved by pharmaceutical strategies against RHAMM and its ligand hyaluronan.
Highlights
Radiotherapy has become standard of care for most breast cancer cohorts [1]
We demonstrate that receptor of hyaluronan-mediated motility (RHAMM) mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival
Patients were stratified into quartiles according to their RHAMM expression for both HMMR probe sets present on the Affymetrix chips
Summary
Radiotherapy has become standard of care for most breast cancer cohorts [1]. Cancer cells can acquire radioresistance with its complementary risk of increased mortality rates [3]. Discovery of targets predicting the response to radiotherapy as well as agents that sensitize cancer cells to ionizing radiation with low side effects, is of great interest. In breast cancer (BC) progesterone or estrogen receptor positive BC subtypes are generally treated by endocrine ablation therapies in combination with chemotherapy and/or radiotherapy. All of those BC subtypes respond to radiation and biomarkers helping to define the radiation regime are urgently needed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
