Navegando por Palavras-chave "Fgf2 Growth Factor"

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    Caracterização In Vitro Do Anticorpo Monoclonal Anti-Fgf2 3F12E7 São Paulo 2016
    (Universidade Federal de São Paulo (UNIFESP), 2017-01-31) Braggion, Camila [UNIFESP]; Moraes, Jane Zveiter De [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The aim of the present study was to characterize the in vitro action of the anti-FGF2 3F12E7 monoclonal antibody (mAb), which showed relevant activity in vivo, reducing tumor vascular density and inhibiting B16F10 melanoma metastasis. We started ana-lyzing the tube formation in matrigel, using human umbilical vein endothelial cells (HUVECs), in the presence or absence of 3F12E7 mAb. The results showed signifi-cant inhibition of the process. By immunoenzymatic and immunofluorescence as-says, it was observed that 3F12E7 mAb binds specifically to HUVECs. It has been found that 3F12E7 mAb inhibited the binding of FGF2 to HUVEC and that anti-FGF2 receptors (FGFR1 and FGFR2) and anti-sindecan-4 interfered with the binding of 3F12E7 mAb to those cells. It was further noted that 3F12E7 mAb interfered in the MAPK signaling pathway by inhibition of the extracellular signal regulated protein ki-nase (phosphorylated ERK), and that such inhibition was specific and increased with-in the first hour of cell treatment. The PI3K signaling pathway, however, does not ap-pear to be influenced by the presence of 3F12E7 mAb, since no significant change in the nitric oxide concentration in the cell culture supernatants was observed. Taken together, the results presented herein suggest that the therapeutic effects of 3F12E7 mAb, observed in vivo, may be due to the inhibition of FGF2 intracellular signaling. The presence of 3F12E7 mAb in the tumor microenvironment seems to prevent the binding of FGF2 to its receptors and, consequently, the formation of the ternary com-plex, responsible for many activities of the angiogenic agent. In addition, our results support the idea of 3F12E7 mAb therapeutic value and still show its potential as a useful tool in tumor microenvironment studies.