Effects of Ionizing Radiation on Human Triple Negative Breast Cancer

Date

2020

Authors

Joshi, Rohan
Choe, Jamie Y.
Chaudhary, Pankaj
Jones, Harlan

ORCID

0000-0002-7803-5962 (Choe, Jamie Y.)

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Abstract

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype which exhibits high rates of metastasis. Due to lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 receptor (HER2), TNBC is not responsive to hormonal treatment and currently lacks targeted therapies. Radiation is an important component of cancer therapy and used clinically in combination with chemotherapy and/or surgery for TNBC patients. Specialized extracellular vesicles called exosomes are involved in intercellular communication and postulated to play roles in tumor metastasis. In this study, we evaluate effects of single-dose ionizing radiation on the proliferation and release of exosomes from three human TNBC cell lines (MDA-MB-231, CAL-51, HCC-1806). TNBC cells were cultured and irradiated with 8.6 Gy. Exosomes were isolated 72h post-irradiation using differential ultracentrifugation and evaluated for size and purity. Nanoparticle tracking analysis (NTA) quantified exosomes released by tumor cells. Western blot confirmed isolation of exosomes by determining expression of established exosome membrane protein markers. Ionizing radiation suppressed proliferation and migration of MDA-MB-231, CAL-51, and HCC-1806 based on in vitro wound-healing (scratch) assays. Total cell counts for irradiated vs. control conditions at the time of exosome isolation were statistically significant in CAL-51 (P=0.0205) and HCC-1806 (P=0.0261). Exosomes released per cell in response to radiation showed inconclusive trends. Our preliminary data demonstrates radiation is capable of depressing TNBC proliferation and warrants further exploration regarding radiation-induced effects on tumor-derived exosomes.

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