title: Blocking FGF2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings.
abstract: Compelling evidence suggests that fibroblast growth factor 2 (FGF2), overexpressed in melanomas, plays an important role in tumor growth, angiogenesis and metastasis. In this study, we evaluated the therapeutic use of a new anti-FGF2 monoclonal antibody (mAb), 3F12E7, using for that the B16-F10 melanoma model. The FGF2 neutralizing effect of this antibody was certified by in vitro assays, which allowed the further track of its possible in vivo application. 3F12E7 mAb could be retained in B16-F10 tumors, as shown by antibody low-pH elution and nuclear medicine studies, and also led to reduction in number and size of metastatic foci in lungs, when treatment starts one day after intravenous injection of B16-F10 cells. Such data were accompanied by decreased CD34(+) tumor vascular density and impaired subcutaneous tumor outgrowth. Treatments starting one week after melanoma cell intravenous injection did not reduce tumor burden, remaining the therapeutic effectiveness restricted to early-adopted regimens. Altogether, the presented anti-FGF2 3F12E7 mAb stands as a promising agent to treat metastatic melanoma tumors in adjuvant settings.
authors.affiliation: Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr Arnaldo 251, 01246-000 São Paulo, SP, Brazil; Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil.
authors.forename: Rodrigo Barbosa
authors.initials: RB
authors.lastname: de Aguiar
authors.affiliation: Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil.
authors.forename: Carolina Bellini
authors.initials: CB
authors.lastname: Parise
authors.affiliation: Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr Arnaldo 251, 01246-000 São Paulo, SP, Brazil.
authors.forename: Carolina Rosal Teixeira
authors.initials: CR
authors.lastname: Souza
authors.affiliation: Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Braggion
authors.affiliation: Laboratório de Biofármacos em Células Animais, Instituto Butantan, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: Quintilio
authors.affiliation: Laboratório de Biofármacos em Células Animais, Instituto Butantan, Avenida Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Moro
authors.affiliation: Centro de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, Trav. Rua Dr. Ovídio Pires de Campos s/n, 05403-010 São Paulo, SP, Brazil.
authors.forename: Fabio Luiz
authors.initials: FL
authors.lastname: Navarro Marques
authors.affiliation: Centro de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, Trav. Rua Dr. Ovídio Pires de Campos s/n, 05403-010 São Paulo, SP, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Buchpiguel
authors.affiliation: Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, Avenida Dr Arnaldo 251, 01246-000 São Paulo, SP, Brazil. Electronic address: rchammas@usp.br.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 862, 04023-062 São Paulo, SP, Brazil. Electronic address: janezvmo@gmail.com.
authors.forename: Jane Zveiter
authors.initials: JZ
authors.lastname: de Moraes
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism; D045744:Cell Line, Tumor; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D016222:Fibroblast Growth Factor 2
keywords: Angiogenesis; FGF2; Melanoma; Metastasis; Monoclonal antibody