INVESTIGADORES
ALANIZ Laura Daniela
artículos
Título:
Hyaluronan preconditioning of monocytes/macrophages affects their angiogenic behavior and regulation of TSG-6 expression associated with the tumor type.
Autor/es:
FIORELLA SPINELLI; DAIANA VITALE; ANTONELLA ICARDI; ILARIA CAON; INA SEVIC; ALEJANDRA BRANDONE; PAULA GIANNONI; VIRGINIA SATURNO; ALBERTO PASSI; MARIANA G. GARCIA; LAURA ALANIZ
Revista:
FEBS JOURNAL
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2019 vol. 17 p. 3433 - 3449
ISSN:
1742-464X
Resumen:
Hyaluronan is a glycosaminoglycan normally present in the extracellular matrix in mosttissues and its levels increased during injury process and in tumor tissues. Hyaluronan is acrucial player in many processes associated with cancer, such as angiogenesis, invasion andmetastasis. However, little has been reported regarding the action of hyaluronan onmonocytes/macrophages in relation to tumor angiogenesis and in consequence in tumordevelopment. In the present study, we investigated the effects of hyaluronan size-dependentdifferences on human monocytes/macrophages angiogenic behavior in colorectal and breastcarcinoma. In vitro, treatment of macrophages with lysates from a breast cancer cell lineplus high molecular weight hyaluronan induced an increased expression of angiogenicfactors: VEGF, IL-8, FGF-2, MMP-2 activity, and incremented endothelial cell migration.Importantly, this treatment diminished the expression of hyaluronan binding protein TSG6,an important regulator of hyaluronan structure and function, besides its anti inflammatory action. Also, these processes were dependent on HA receptors CD44 andTLR4 expression, but not RHAMM. The in vivo model confirmed these results,macrophages primed with high molecular weight hyaluronan and inoculated in humanbreast cancer xenograft tumor incremented blood vessel formation and diminished TSG-6levels. In contrast and unexpectedly these effects triggered by high molecular weighthyaluronan on monocytes/macrophages were not observed in colorectal carcinoma contextboth in vitro or in vivo. Taken together, these results indicate that high molecular weight hyaluronan might prime and regulates the angiogenic action of macrophages, in part bydecreasing TSG-6 expression and importantly this action depends on the tumor milieu