Sulfated hyaluronan: antitumor and antiangiogenic effect on tumor cells and monocytes/macrophages in breast cancer context.

SPINELLI FS; PLUDA S; VITALE DL; ROSALES P; ICARDI A; SEVIC I; GARCIA M; GALESSO D; ALANIZ L

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia (SAIC SAI SAFIS); 2020

Breast carcinoma is one the most frequent types of cancer. The potentiation of immune action again this tumor will be a promising therapeutic option. Monocytes/macrophages (Mo/MØ) are critical modulators of the tumor microenvironment. Chemically modified hyaluronan (HA) like sulfated hyaluronan (sHA) are biomaterials that can work as a possible adjuvant therapy. It demonstrated that sHA can inhibit hyaluronidases and have a potent antitumor and antiangiogenic action in prostate and bladder cancer cells. In this sense, the aim is to evaluate sHA effect on breast tumor cells and on Mo/MØ in tumor context. M&M. sHA (sHA1 and sHA3) were synthesized from the tetrabutyl ammonium salt of HA in Fidia Farmaceutici s.p.a. Cells: i)human breast cancer cell line (MDAMB-231), ii)human microvascular endothelium (HMEC-1) and iii)Mo/MØ (obtain from human peripheric blood with Ficoll/Percoll). MTS assay was used to measure cell viability. LDH assay was used to measure cytotoxicity. TGFβ1 and VEGF levels were measured by ELISA. VEGF, FGF-2 and IL8 levels were measured by qPCR. Cell migration was evaluated using a modified Boyden chamber. Mammospheres were obtained through hanging drop. In vivo experiments: Mo/MØ pulsed with sHA were inoculated in MDA-MB-231 xenograft mice model. Tumors were fixed and stained with: i)Lectin GSLI-FITC for vasculature detection and ii)HA and TSG-6. Results. sHA treatments in MDA-MB-231: enhanced cytotoxicity and decreased cell viability, mammospheresize, VEGF levels and HMEC-1 migration. Whereas, sHA treatments in Mo/MØ in breast tumor context increased Mo/MØ viability, decreased TGFβ1 total levels, modulated TSG-6 and decreased the expression of angiogenic factors and HMEC-1 migration. Even more, Mo/MØ primed with sHA and inoculated breast tumor model decreased blood vessel formation, TSG-6 and HA levels. Conclusion. sHA showed an antitumor and antiangiogenic role in breast tumor cells, as well as in Mo/MØ in breast cancer context.