IS HYALURONAN A TUMOR PROMOTER? DIFFERENT ACTION ON ANGIOGENIC BEHAVIOR OF MACROPHAGES IN BREAST AND COLON CANCER HUMAN MODEL.

FIORELLA SPINELLI; DAIANA VITALE; ANTONELLA ICARDI; MARIANA GARCÍA; LAURA ALANIZ

Ciudad de Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC; SAIB; SAI; SAA; SAB; SAFE; SAFIS; SAH; SAP

Hyaluronan(HA) is a glycosaminoglycan present in the extracellular matrix and acts as a modulator of immune and angiogenic responses. At homeostasis, high-molecular weight (HMW) HA is predominant whereas the low-molecular weight (LMW) form is present in inflammation. HA in tumor microenvironment is signal for recruiting tumor associated macrophages, that could regulate angiogenesis. Aim: To evaluate the effect of exogenous HA (HMW, LMW) on human monocytes/macrophages (MO) and their angiogenic behavior in breast and colon carcinoma. Methods: MDA-MB 231 or LoVo from human breast and colorectal carcinoma tumor lysates (TL) were prepared by freeze?thaw cycles. MO from PBMCs were pulsed with TL plus HA(20ug/ml) LMW(@ 1,5x106Da) or HMW(@2x105Da) for 24h. MO were characterized with CD14, HLA, CD80 and CD206 by flow cytometry. VEGF levelwas evaluated by ELISA assay. For the in vivo xenograft mouse model MDA-MB-231 or LoVo cells were inoculated in the flank of Nu/nu mice. After 9 days, MO pulsed or not with HA were inoculated sc next to the tumor. Tumor volume was measured 3 times/week. Animals were euthanatized, tumors were fixed and stained with Lectin GSLI-FITC and DAPI for vasculature detection. Results: The HA treatments did not modify the expression of MO cell surface markers. VEGF biosynthesis levels increased when MO were treated with MDA TL plus HA HMW in comparison to MDA TL alone and plus HA LMW. However, VEGF levels showed no significative difference in LoVo TL treatments. In the MDA model, mice inoculated with MO plus HA HMW increased tumor volume and its vasculature. While in the LoVo model no differences were found between groups. Conclusion: HA HMW modulates MO angiogenic behavior in breast carcinoma. However, HMW HA is unable to do the same action in colon carcinoma context. Our results provide evidence that HA modulation of this cells depends not only of its molecular weight but also of the tumor context.