Abstract

High glucose generates a pro-inflammatory stromal microenvironment which favors the expression of malignancy traits in breast tumor cells. Tobar N., Kallens V., Bidegain A., Ponce I. Porras O. and Martínez J. Cell Biology Lab. INTA University of Chile. ([email protected]) Introduction: Human tumors develop under the essential influence of a cellular stroma. Paracrine signals originated from tumor-associated stroma can establish an inflammatory microenvironment which modulates behavior of carcinoma cells. In addition, it is well known that most solid tumors have high rates of glucose uptake and acquire a desmoplastic phenotype. In this work we studied the influence of stromal glucose exposure in the generation of inflammatory intermediates and expression of malignant markers in epithelial cells. Material and Methods: Mammary stromal RMF-EG cells were grown in low (5.5 mM) or high (25 mM) extracellular glucose. Cellular redox state in living RMF cells were performed using Hyper, a FRET nanosensor that measures intracellular hydrogen peroxide. Cell migration was assayed by Transwell methods. COX-2, IL-1β and IL1-R1 expression was evaluated by qPCR and western blot. Results: Our results suggest that high glucose generates an oxidative and inflammatory stromal environment characterized by a stimulus on the IL1--dependent expression of COX-2 that predisposes epithelial motility. We demonstrate the existence of a glucose-dependent stromal stimulus on IL1-R1 receptor expression and a higher expression of IL1-R1 in human samples of high grade mammary tumors. Funding: PAI 77170001