Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor

Marcella Marcellini, Naomi De Luca, Teresa Riccioni, Alessandro Ciucci, Angela Orecchia, Pedro Miguel Lacal, Federica Ruffini, Maurizio Pesce, Francesca Cianfarani, Giovanna Zambruno, Augusto Orlandi, Cristina Maria Failla

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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.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalAmerican Journal of Pathology
Volume169
Issue number2
DOIs
Publication statusPublished - Aug 2006

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Melanoma
Neoplasm Metastasis
Growth
Transgenic Mice
Neoplasms
Genetically Modified Animals
Keratin-14
Pathologic Neovascularization
Hematopoietic Stem Cell Mobilization
Skin
Experimental Melanomas
Placenta Growth Factor
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A
Extracellular Matrix
Bone Marrow
Phenotype
Lung

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor. / Marcellini, Marcella; De Luca, Naomi; Riccioni, Teresa; Ciucci, Alessandro; Orecchia, Angela; Lacal, Pedro Miguel; Ruffini, Federica; Pesce, Maurizio; Cianfarani, Francesca; Zambruno, Giovanna; Orlandi, Augusto; Failla, Cristina Maria.

In: American Journal of Pathology, Vol. 169, No. 2, 08.2006, p. 643-654.

Research output: Contribution to journalArticle

Marcellini, Marcella ; De Luca, Naomi ; Riccioni, Teresa ; Ciucci, Alessandro ; Orecchia, Angela ; Lacal, Pedro Miguel ; Ruffini, Federica ; Pesce, Maurizio ; Cianfarani, Francesca ; Zambruno, Giovanna ; Orlandi, Augusto ; Failla, Cristina Maria. / Increased melanoma growth and metastasis spreading in mice overexpressing placenta growth factor. In: American Journal of Pathology. 2006 ; Vol. 169, No. 2. pp. 643-654.
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