Ionizing radiation and metastasis: the dark side of a keystone treatment in cancer

VEDOYA G, MOHAMAD N, TAQUEZ DELGADO M, GALARZA T. BERGOC R, CRESCENTI E, CRICCO G, MARTIN G

Cape Town

Congreso; 14th International Congress of the International Radiation Protection Association; 2016

International Radiation Protection Association

Radiation therapy is an important therapeutic tool in clinical oncology. Conventional radiation therapy for breast cancer after surgery is delivered in fractionated doses to treat post-mastectomy chest wall, or to treat the remaining whole breast post conservative surgery. Photon radiation has proved its benefits in overall survival, nonetheless some patients present local recurrences or metastases. Experimental evidence suggests that ionizing radiation might promote migration and invasion of tumoral surviving cells by intricate implications in the micro-environment, proteases secretion, and induction of epithelial mesenchymal transition. In this work we conducted in vitro and in vivo studies to evaluate the effect of 2 Gy fraction of gamma radiation in different biological responses related to metastasis formation employing the triple negative breast cancer cell line MDA-MB-231.When we assessed in vitro clonogenic growth we found that after 24 h of irradiation, colony formation was decreased to 22% of control values, but then clonogenicity increased for the next two weeks. In addition, conditioned media from irradiated normal mammary epithelial cells MCF-10A also increased significantly irradiated MDA-MB-231 cells clonogenic proliferation. Other features related to invasive phenotype as gelatinolytic activity and cell migration were also enhanced.We also carried out in vivo experiments by implanting 2 Gy irradiated and non irradiated MDA-MB-231 xenografts in nude mice. Irradiated tumors evidenced larger volume than non irradiated controls after 30 days. Ex vivo analysis of xenografts showed a higher mitotic index and PCNA expression in irradiated than in non irradiated tumors, as well as higher intratumoral vascularity evaluated by hematoxilin and CD34 staining. Lungs of mice bearing irradiated xenografts sowed a higher number of metastatic foci than lung from mice with control tumors.A better knowledge of radioinduced biological responses could lead to new therapeutic strategies for enhancing antitumor effectiveness