Spinelli, Fiorella Mercedes; Vitale, Daiana Luján; Icardi, Antonella; Caon, Ilaria; Brandone, Alejandra; Giannoni, Paula; Saturno, Virginia; Passi, Alberto; García, Mariana; Sevic, Ina; Alaniz, Laura
Resumen:
Hyaluronan is a glycosaminoglycan normally present in the extracellular
matrix in most tissues. Hyaluronan is a crucial player in many processes
associated with cancer, such as angiogenesis, invasion, and metastasis. However,
little has been reported regarding the action of hyaluronan on monocytes/
macrophages (Mo/MØ) in tumor angiogenesis and its consequences on
tumor development. In the present study, we investigated the effects of
hyaluronan of different sizes on human Mo/MØ angiogenic behavior in colorectal
and breast carcinoma. In vitro, the treatment of Mo/MØ with lysates
and conditioned media from a breast but not from colorectal carcinoma cell
line plus high-molecular weight hyaluronan induced: (a) an increased expression
of angiogenic factors VEGF, IL-8, FGF-2, and MMP-2, (b) an
increased endothelial cell migration, and (c) a differential expression of
hyaluronan-binding protein TSG-6. Similar results were observed in Mo/
MØ derived from breast cancer patients treated with tumor lysates. Besides,
macrophages primed with high-molecular weight hyaluronan and inoculated
in human breast cancer xenograft tumor increased blood vessel formation
and diminished TSG-6 levels. In contrast, the effects triggered by highmolecular
weight hyaluronan on Mo/MØ in breast cancer context were not
observed in the context of colorectal carcinoma. Taken together, these results
indicate that the effect of high-molecular weight hyaluronan as an inductor
of the angiogenic behavior of macrophages in breast tumor context is in part
consequence of the presence of TSG-6.
