The secretome of irradiated non-tumorigenic mammary cells MCF-10A elicits DNA damage in MCF-7 and MDA-MB-231 breast cancer cells

VEDOYA GUADALUPE; MOHAMAD NORA; CRICCO GRACIELA; BOMBEN ANA; LOPEZ NIGRO MARCELA; MARTIN GABRIELA

Congreso; IRPA15, 15th International Congress of the International Radiation Protection Association; 2021

International Radiation Protection Association

Radiotherapy is used as an adjuvant treatment post-surgery in breast cancer because some foci of cancer cells may linger at the remaining breast tissue or the mastectomy site. It was long accepted that the lethal effects of ionizing radiation occur as a result of damage to the DNA in irradiated (IR) cells. However, DNA damage response mechanisms are activated and may promote cell survival with efficient repair or with genomic alterations. Chromosomal aberrations are frequent in surviving cells and may enhance the chromosomal instability (CIN) which has been associated with increased risk of recurrence and metastasis. Besides, scientific evidence indicates that intercellular communication can affect the response in IR cells and even cause damage non-irradiated (N-IR) cells. In this study, we evaluated the effect of the secretome of non-tumorigenic mammary epithelial cells (MCF-10A) on proliferation and biological responses related to DNA damage in breast cancer cells (MCF-7 and MDA-MB-231). Our findings showed that conditioned media from IR and N-IR MCF-10A cells produces cycles of DNA double-strand breaks in N-IR and IR tumor cells leaving them with residual damage. CIN markers (micronuclei, nucleoplasmic bridges and nuclear buds) were also increased in both IR and N-IR tumor cells, being the effect of conditioned media from IR MCF-10A greater in many cases. Besides, the clonogenic survival of tumor cells was differentially modulated by conditioned media from MCF-10A: it was decreased in MCF-7 and enhanced in MDA-MB-231 cells. These results evoke the relevance of tumor-host interaction in tumor behavior and the response to radiotherapy.