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FEBS J ; 286(17): 3433-3449, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31044513

RESUMO

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.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Moléculas de Adesão Celular/genética , Neoplasias Colorretais/metabolismo , Ácido Hialurônico/farmacologia , Células Precursoras de Monócitos e Macrófagos/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Animais , Neoplasias da Mama/patologia , Carcinoma/patologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Meios de Cultivo Condicionados/farmacologia , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Células Precursoras de Monócitos e Macrófagos/citologia , Células Precursoras de Monócitos e Macrófagos/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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