Inflammatory Response to a High Radiation Dose in Breast Cancer

Background: Radiation therapy (RT) is an essential treatment modality used for breast cancer (BC) care. Radiations can stimulate the immune system via the early activation of cytokine cascades, which can greatly affect cellular radio-sensitivity. Our aim is to analyze inflammatory response induced by high ionizing radiation (IR) doses, generated by intraoperative radiotherapy (IORT) treatment, to identify several potential targets that may influence cell radio-response. Methods: MCF10, MCF7 and MDA-MB231 BC cell lines have been exposed to high IR (23 Gray and 9 Gray), delivered by IORT treatments. Conditioned media (CM) were assayed at the time points: 0’, 30’, 1, 3, 6, 24, 48, and 72 hours, for production of cytokines, chemokines and growth factors by using Luminex technology. Results: We observed a very low cytokine concentration in MCF7 CM and a greater expression, of TH1 and TH2 cytokines, IL-7, G-CSF and MCP-1 in MCF10A CM. MDA-MB231 CM showed a reduced expression of TH1 and TH2 cytokines, IL-7, G-CSF, MCP-1 and an up-regulation of GM-CSF, IL-6 and IL-8 factors. Conclusions: Our results indicate that cytokine production in most cases is dose independent and time and cell type dependent. In particular, an over production at 24 hours after IORT treatment was observed. In addition, we speculate that MCF10A cells potentially exhibit an increased capacity to activate the immune system after IR exposure, and that MDAMB231 cells could have a role in radio-resistance phenotype through IL-6 and IL-8 high production activated by IR.