The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR- 1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

Ceci, C., Atzori, M.g., Lacal, P.m., Graziani, G. (2020). Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic cancer models. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(4) [10.3390/ijms21041388].

Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic cancer models

Ceci C.;Graziani G.
2020-01-01

Abstract

The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR- 1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.
2020
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14 - FARMACOLOGIA
English
Angiogenesis; Cancer; Flt-1; Immune escape; Melanoma; Metastasis; PlGF; VEGF-A; VEGFR-1
Ceci, C., Atzori, M.g., Lacal, P.m., Graziani, G. (2020). Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic cancer models. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(4) [10.3390/ijms21041388].
Ceci, C; Atzori, Mg; Lacal, Pm; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/248974
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