Placenta growth factor (PlGF) is a key regulator of pathological angiogenesis and its overexpression has been linked to neoplastic progression. To assess whether PlGF could have a role in malignant mesothelioma (MM), we analyzed the expression of PlGF, VEGF, and their cognate receptors (VEGF-R1 and VEGF-R2) and co-receptors (neuropilin-1 and neuropilin-2) in MM cell lines as well as in resected MM tissues, hyperplastic/reactive mesothelium and normal mesothelium. MM cell cultures expressed both ligands and the associated receptors to a variable extent and released different amounts of PlGF. As assessed by immunohistochemistry, PlGF expression was switched on in hyperplastic/reactive compared to normal mesothelium. Moreover, 74 and 94 percent of MM tissues overexpressed PlGF and VEGF-R1, respectively (p<0.05 MM vs normal mesothelium). Administration of recombinant PlGF-2 did not elicit a significant stimulation of MM cell growth, while it was associated with a transient phosphorylation of Akt, suggesting that PlGF-2 could activate downstream effectors of proliferative and cytoprotective signals via VEGF-R1 in MM cells. Indeed, the administration of an anti-PlGF antibody was found to cause a significant reduction of MM cell survival. In conclusion, our data demonstrate that, by acting as a survival factor, PlGF can play a role which goes beyond the stimulation of angiogenesis in MM. This evidence could help the rational design of new therapeutic interventions for this aggressive tumor.

ALBONICI BOVE, L., Doldo, E., Palumbo, C., Orlandi, A., Bei, R., Pompeo, E., et al. (2009). Placenta growth factor is a survival factor for human malignant mesothelioma cells. INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 22(2), 389-401.

Placenta growth factor is a survival factor for human malignant mesothelioma cells

ALBONICI BOVE, LOREDANA;PALUMBO, CAMILLA;ORLANDI, AUGUSTO;BEI, ROBERTO;POMPEO, EUGENIO;MINEO, TOMMASO CLAUDIO;MODESTI, ANDREA;MANZARI, VITTORIO
2009

Abstract

Placenta growth factor (PlGF) is a key regulator of pathological angiogenesis and its overexpression has been linked to neoplastic progression. To assess whether PlGF could have a role in malignant mesothelioma (MM), we analyzed the expression of PlGF, VEGF, and their cognate receptors (VEGF-R1 and VEGF-R2) and co-receptors (neuropilin-1 and neuropilin-2) in MM cell lines as well as in resected MM tissues, hyperplastic/reactive mesothelium and normal mesothelium. MM cell cultures expressed both ligands and the associated receptors to a variable extent and released different amounts of PlGF. As assessed by immunohistochemistry, PlGF expression was switched on in hyperplastic/reactive compared to normal mesothelium. Moreover, 74 and 94 percent of MM tissues overexpressed PlGF and VEGF-R1, respectively (p<0.05 MM vs normal mesothelium). Administration of recombinant PlGF-2 did not elicit a significant stimulation of MM cell growth, while it was associated with a transient phosphorylation of Akt, suggesting that PlGF-2 could activate downstream effectors of proliferative and cytoprotective signals via VEGF-R1 in MM cells. Indeed, the administration of an anti-PlGF antibody was found to cause a significant reduction of MM cell survival. In conclusion, our data demonstrate that, by acting as a survival factor, PlGF can play a role which goes beyond the stimulation of angiogenesis in MM. This evidence could help the rational design of new therapeutic interventions for this aggressive tumor.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/04 - Patologia Generale
English
Con Impact Factor ISI
cell proliferation; time factors; cell line; gene expression regulation, neoplastic; vascular endothelial growth factor a; epithelium; mesothelioma; vascular endothelial growth factor receptor-2; pleural neoplasms; cell death; humans; vascular endothelial growth factor receptor-1; neuropilin-2; cell survival; hyperplasia; rna, messenger; pregnancy proteins; recombinant proteins; neuropilin-1; phosphorylation; proto-oncogene proteins c-akt; neovascularization, pathologic
ALBONICI BOVE, L., Doldo, E., Palumbo, C., Orlandi, A., Bei, R., Pompeo, E., et al. (2009). Placenta growth factor is a survival factor for human malignant mesothelioma cells. INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 22(2), 389-401.
ALBONICI BOVE, L; Doldo, E; Palumbo, C; Orlandi, A; Bei, R; Pompeo, E; Mineo, Tc; Modesti, A; Manzari, V
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/14849
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