title: Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor.
abstract: Placenta growth factor (PlGF), a member of the vascular endothelial growth factor family, plays an important role in adult pathological angiogenesis. To further investigate PlGF functions in tumor growth and metastasis formation, we used transgenic mice overexpressing PlGF in the skin under the control of the keratin 14 promoter. These animals showed a hypervascularized phenotype of the skin and increased levels of circulating PlGF with respect to their wild-type littermates. Transgenic mice and controls were inoculated intradermally with B16-BL6 melanoma cells. The tumor growth rate was fivefold increased in transgenic animals compared to wild-type mice, in the presence of a similar percentage of tumor necrotic tissue. Tumor vessel area was increased in transgenic mice as compared to controls. Augmented mobilization of endothelial and hematopoietic stem cells from the bone marrow was observed in transgenic animals, possibly contributing to tumor vascularization. The number and size of pulmonary metastases were significantly higher in transgenic mice compared to wild-type littermates. Finally, PlGF promoted tumor cell invasion of the extracellular matrix and increased the activity of selected matrix metalloproteinases. These findings indicate that PlGF, in addition to enhancing tumor angiogenesis and favoring tumor growth, may directly influence melanoma dissemination.
authors.affiliation: Laboratory of Experimental Angiogenesis, Sigma Tau, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Marcellini
authors.forename: Naomi
authors.initials: N
authors.lastname: De Luca
authors.forename: Teresa
authors.initials: T
authors.lastname: Riccioni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ciucci
authors.forename: Angela
authors.initials: A
authors.lastname: Orecchia
authors.forename: Pedro Miguel
authors.initials: PM
authors.lastname: Lacal
authors.forename: Federica
authors.initials: F
authors.lastname: Ruffini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
authors.forename: Francesca
authors.initials: F
authors.lastname: Cianfarani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Failla
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008545:Melanoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009389:Neovascularization, Pathologic; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D000072483:Placenta Growth Factor; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1