HYALURONAN-CD44 INTERACTION DURING TUMOR DEVELOPMENT AND THEIR ROLE AS MODULATOR OF IMMUNE SYSTEM

VITALE DAINA; SPINELLI FIORELLA; DEMARCHI G; BOLNTRADE MARCELA; CRISTINA C; ALANIZ L

Ciudad de Bs. As.

Congreso; IV LASID- LXIIISAI- II FAIC Meeting; 2015

Sociedad Argentina de Inmunología (SAI)

BackgroundThe extracellular matrix(ECM) induce signals that lead to unregulated cell behavior, affecting immune responses[1]. Since immune modulation modify tumor progression[2], the factors that regulate it, can affect their development. Among the components of the ECM, hyaluronan(HA) is differentially expressed in various tumors, and the interaction with CD44, HA major receptor, can promote metastasis, angiogenesis and immune modulation[3]. The aim of this project is to study how HA-CD44 interaction modulates intracellular signaling pathways implicated in angiogenesis and immune response in the tumor microenvironment.MethodsMurine tumor cell lines (EL4, MC38, K12) were treated with HA (20 and 100 µg/ml). Angiogenic and proliferative capacity of cells were evaluated. VEGF, VEGFR-1, SDF-1α, CXCR4, IL-10, IL-8 and β-catenin mRNA expression levels were analyzed by RT-qPCR. Proteins levels were measured by ELISA and Western Blot. ResultsHA treatment enhanced significantly genes expression in doses dependent form in all factors described above. Similar results were observed in protein levels analyses of these factors. ConclusionSeveral studies determined that HA could modulate angiogenesis, but the mechanisms involved in this process is not yet clear. This study present evidence about the signaling pathways implicated in HA modulation of angiogenesis and immune responses in tumor microenvironment, providing important information at the moment of designing new therapeutic strategies.