INVESTIGADORES
ALANIZ Laura Daniela
congresos y reuniones científicas
Título:
HYALURONAN PRECONDITIONING OF MONOCYTES/MACROPHAGES AFFECTS THEIR ANGIOGENIC BEHAVIOR AND REGULATION OF TSG-6 EXPRESSION IN BREAST CANCER.
Autor/es:
FIORELLA SPINELLI; VITALE DAINA; ANTONELLA ICARDI; ILARIA CAON; ALBERTO PASSI; MARIANA G. GARCIA; INA SEVIC; ALANIZ L
Reunión:
Conferencia; 12th International Conference on Hyaluronan; 2019
Institución organizadora:
International Society for Hyaluronan Sciences
Resumen:
Introduction. Hyaluronan(HA) is a crucial player in many processes associated with cancer, such as angiogenesis, invasion and metastasis1. HA functions are well known to be size-dependent1. HA binds several cell surface receptors and binding proteins, for example TSG-62. TSG-6 allows the formation of HA crosslinking with other matrix components, such as IαI heavy chains which allows stabilization and structural integrity of the extracellular matrix. Monocytes/macrophages(Mo/MØ) are critical modulators of the tumor microenvironment, although its behavior differs considerably among tumors2. Mo/MØ bind HA which induces intracellular signals; however, the role that different sized HA plays on Mo/MØ behavior in the presence of tumor factors is not well known, defining their anti or pro-tumor effect3. Aim. The aim of this study was to evaluate the effects of hyaluronan size-dependent differences on human monocytes/macrophages angiogenic behavior in breast carcinoma and its association with TSG-6 expression.M&M. For the in vitro experiments, Mo/MØ derived from human PBMCs were treated with supernatants or lysates derived from MDA-MB-231 and LMW HA or HMW HA(20 ug/ml). Mo/MØ derived from breast cancer patients were treated with tumor tissue or and LMW HA or HMW HA(20 ug/ml) and from normal tissue adjacent to the tumor. VEGF, FGF-2 and IL8 mRNA levels were measured by qPCR. TSG-6 was measured in Mo/MØ supernatants by Western blot. For the in vivo experiments, Mo/MØ pulsed or/not with HA were inoculated in MDA-MB-231 xenograft mice model. Animals were euthanatized at day 29, tumors were fixed and stained with: i)Lectin GSLI-FITC for vasculature detection and ii)HA-binding protein and Ab-anti-TSG-6.Results. In vitro treatment of Mo/MØ with breast tumor lysates or conditioned media from a breast cancer cell line plus HMW HA induced an increased expression of angiogenic factors: VEGF, IL-8 and FGF-2. Besides, we observed a modulation of HA binding protein TSG-6 levels in the supernatants of Mo/MØ treated with breast cancer cell line and lysates from breast carcinoma patient samples. 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.Conclusion. Taken together these results indicate that the effect of HMW HA as inductor of the angiogenic behavior of macrophages in tumor context is in part consequence of the presence of TSG-6.Funding Sources.GLYCAN 645756, European Commission. Fundación Roemmers. SIB UNNOBA. References. 1.Spinelli et al., Clin Transl Immunology, 2015. ? 2.Day & Milner, MATBIO, 2018. ? 3.Mantovani et al., Nat Rev Clin Oncol, 2017.