Breast cancer: hyaluronan preconditioning of monocytes/macrophages affects angiogenesis and TSG-6 expression.

SPINELLI, FIORELLA M.; VITALE, DAIANA L.; ICARDI, ANTONELLA; CAON, ILARIA; BRANDONE, ALEJANDRA; GIANNONI, PAULA; PASSI, ALBERTO; GARCÍA, MARIANA; SEVIC, INA; ALANIZ, LAURA

Ciudad Autónoma de Buenos Aires

Simposio; Glycobiology Symposium "GLYCOAR 2019"; 2019

Hyaluronan(HA) is a crucial player in many processes associated with cancer, such as angiogenesis, invasion and metastasis. HA binds to TSG-6 which allows it to crosslink with other matrix components. Monocytes/macrophages(Mo/MØ) are critical modulators of the tumor microenvironment, although its behavior differs considerably among tumors. The aim of this study was to evaluate the effects of HA on human Mo/MØ angiogenic behavior in breast carcinoma and its association with TSG-6 levels. Mo/MØ derived from human PBMCs were treated with supernatants or lysates derived from MDA-MB-231. VEGF, FGF-2 and IL8 mRNA levels were measured by qPCR. TSG-6 was measured by Western blot. Mo/MØ pulsed or/not with HA were inoculated in MDA-MB-231 xenograft model. Tumors were fixed and stained with: GSLI-FITC for vasculature detection and HA-binding protein and Ab-anti-TSG-6. Treatment of Mo/MØ with tumor lysates or conditioned media from MDA-MB-231 plus HMW HA induced an increased expression of angiogenic factors: VEGF, IL-8 and FGF-2. Besides, in these treatments we observed a modulation of TSG-6 levels in the supernatants of Mo/MØ. Even more, Mo/MØ primed with HMW HA and inoculated in human breast cancer xenograft tumor incremented blood vessel formation and diminished TSG-6 levels. These results indicate that the effect of HMW HA as inductor of the angiogenic behavior of macrophages in breast tumor is in part consequence of the presence of TSG-6.