Efeito biológico da proteína pentraxina 3 sobre fibrossarcomas

• Ano de defesa: 2018
• Autor(a) principal: Priscila Fabiana Rodrigues
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Genética
• Link de acesso: http://hdl.handle.net/1843/BUOS-B5SK2Z

Soluble pattern recognition receptor Pentraxin-3 (PTX3) is an acute phase inflammatory protein, with an important and non-redundant role in innate immunity, matrix deposition, female fertility, angiogenesis and inflammation. In cancer, PTX3 presents a duality of actions being oncopromoter in some cases, however, oncossupressor in others. PTX3 binding to Fibroblast Growth Factors 2 and 8 (FGF2 e 8) inhibits the signaling via FGF/FGFR and the proliferative and proangiogenic activities exerted by these factors, and it is one of the mechanisms that underline PTX3 antitumor activity. Fibrosarcomas are malignant soft tissue mesenchymal tumors in which the FGF/FGFR pathway plays a key role in onset and progression. The objective of this work was to analyze the effect of PTX3 on the proliferation of fibrosarcoma cells in vitro and the progression of this tumor type in vivo. Treatment of MC17-51 and SaIN murine fibrosarcoma cells in vitro with the recombinant murine Pentraxin 3 protein (rmPTX3) pointed to a proproliferative action of pentraxin. However, when murine MC17-51 and human HT-1080 fibrosarcoma cells were transfected with a plasmid for enhanced PTX3 expression, the overexpression of the pentraxin significantly reduced cell proliferation, clonogenic potential and anchorage independent growth of these cells in vitro. In vivo assays, overexpression of PTX3 compromised the growth of both human and murine tumors induced in NOD/SCID and C57BL/6 mice respectively by subcutaneous inoculation of HT-1080 and MC17-51 PTX3 overexpressing cells. One of the mechanisms involved in the oncosuppressive effect observed was the inhibition of the FGF/FGFR signaling pathway, since a reduction in the activation of the downstream molecules ERK and AKT, was observed. Our data not only contribute to the characterization of the role of PTX3 in the biology of tumors but also signal the need for new studies aiming to evaluate the potential of PTX3 as a biomarker of sarcomas progression and also as a pharmacological tool for the treatment of these neoplasms.