2024-03-29T14:58:49Zhttps://gredos.usal.es/oai/requestoai:gredos.usal.es:10366/1406782022-02-07T15:45:42Zcom_10366_133043com_10366_4576com_10366_3823com_10366_4577col_10366_135272col_10366_4578
C3G promotes a selective release of angiogenic factors from activated mouse platelets to regulate angiogenesis and tumor metastasis
Martín-Granado, Víctor
Ortiz-Rivero, Sara
Carmona, Rita
Gutiérrez-Herrero, Sara
Barrera, Mario
San-Segundo, Laura
Sequera, Celia
Perdiguero, Pedro
Lozano, Francisco
Martín-Herrero, Francisco
González-Porras, José Ramón
Muñoz-Chápuli, Ramón
Porras, Almudena
Guerrero, Carmen
C3G
Platelet secretome
Angiogenesis
Vamp-7
Metastasis
[EN]Previous observations indicated that C3G (RAPGEF1) promotes α-granule release,
evidenced by the increase in P-selectin exposure on the platelet surface following
its activation. The goal of the present study is to further characterize the potential
function of C3G as a modulator of the platelet releasate and its implication in the
regulation of angiogenesis.
Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from
activated transgenic C3G and C3GΔCat platelets. Accordingly, the secretome from both
transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro
capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells)
and by two in vivo models of heterotopic tumor growth. In addition, transgenic C3G
expression in platelets greatly increased mouse melanoma cells metastasis. Moreover,
immunofluorescence microscopy showed that the pro-angiogenic factors VEGF and
bFGF were partially retained into α-granules in thrombin- and ADP-activated mouse
platelets from both, C3G and C3GΔCat transgenic mice. The observed interaction
between C3G and Vesicle-associated membrane protein (Vamp)-7 could explain these
results. Concomitantly, increased platelet spreading in both transgenic platelets upon
thrombin activation supports this novel function of C3G in α-granule exocytosis.
Collectively, our data point out to the co-existence of Rap1GEF-dependent and
independent mechanisms mediating C3G effects on platelet secretion, which regulates
pathological angiogenesis in tumors and other contexts. The results herein support
an important role for platelet C3G in angiogenesis and metastasis.
2020-01-24T10:07:51Z
2020-01-24T10:07:51Z
2020-01-24T10:07:51Z
2017
info:eu-repo/semantics/article
Martín-Granado et al. (2017). C3G promotes a selective release of angiogenic factors from activated mouse platelets to regulate angiogenesis and tumor metastasis. Oncotarget, 8 (67), pp. 110994-111011
http://hdl.handle.net/10366/140678
10.18632/oncotarget.22339
1949-2553
spa
https://doi.org/10.18632/oncotarget.22339
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional