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 high-molecular 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.

Hyaluronan preconditioning of monocytes/macrophages affects their angiogenic behavior and regulation of TSG-6 expression in a tumor type-specific manner

Vitale D. L.;Caon I.;Passi A.;
2019-01-01

Abstract

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 high-molecular 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.
2019
2019
angiogenesis; breast carcinoma; colorectal carcinoma; hyaluronan; monocytes/macrophages; TSG-6; Animals; Breast Neoplasms; Carcinoma; Cell Adhesion Molecules; Cell Line, Tumor; Colorectal Neoplasms; Culture Media, Conditioned; Female; Fibroblast Growth Factor 2; Humans; Hyaluronic Acid; Interleukin-8; Matrix Metalloproteinase 2; Mice; Monocyte-Macrophage Precursor Cells; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
Spinelli, F. M.; Vitale, D. L.; Icardi, A.; Caon, I.; Brandone, A.; Giannoni, P.; Saturno, V.; Passi, A.; Garcia, M.; Sevic, I.; Alaniz, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2144574
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