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Endothelial cell activation on 3D-matrices from PDGF stimulated fibroblasts is mediated by Snail1

AuthorsHerrera, Mercedes; García, Vanesa; Larriba, María Jesús ; Casal, J. Ignacio ; García de Herreros, Antonio; Bonilla, Félix
Issue Date2015
CitationV Encuentro Científico de Jóvenes Investigadores de la RTICC (2015)
AbstractVascular network tormation is regulated by signals trom the microenvironment, including the extracellular matrix (ECM) characteristics. It is not clear how endothelial cells integrate these signals to drive the capillary morphogenesis. The aim of this study was to analyze the effects of ECM derived from activated fibroblasts on the angiogenesis process. PDGF stimulated fibroblasts revealed a parallel pattern of ECM fibers. HUVECs seeded on ECM from PDGF stimulated fibroblasts showed increased tubulogenesis compared to ECM from non-stimulated fibroblasts. Angiogenesis markers were increased in HUVECs from PDGFderived ECMs. We recently proposed Snaill as a marker of activated fibroblasts. To study a putative role of fibroblastic Snail on ECM, we also generated ECMs using control or Snail-KO MEFs with or without PDGF. In PDGF-treated control MEFs, ECM fibers were oriented anisotropically, while, PDGF treatment contained fewer fibers and failed to reorganize them in ECMs from Snail-KO MEFs. HUVECs seeded on Snaill KO MEFs ECMs showed a reduction on capillaries structures regarding control MEFs ECMs. A decrease of endothelial markers was observed in HUVECs seeded on Snaill KO MEFs ECMs. The expression of DDR2 was also downregulated in these ECMs. In addition, HUVECs seeded on ECMs from control MEFs, showed a decreased adhesion and enhanced proliferation when compared with HUVECs grown on Snaill-KO MEFs ECMs. Organotypic ce-culture of control MEFs showed an increased number of invading HUVECs, with individual and collective invasion, regarding Snaill KO MEFs gels with few cells invading individually. PDGF treated control MEFs gels revealed enhanced collective invasion with cells migrating as a cohort, connpared to non-treated control MEFs gels. No PDGF effects were observed in HUVECs seeded on gels derived from Snaill KO fibroblasts. Together these experiments demonstrate that ECMs from PDGF stimulated fibroblasts increase angiogenic abilities of endothelial cells in a Snaill-dependent manner. Future studies will include analysis of Snaill expression in stroma and angiogenesis markers in tissue from colon cancer patients.
DescriptionResumen del póster presentado al V Encuentro Científico de Jóvenes Investigadores de la Red Temática de Investigación Cooperativa en Cáncer, celebrado en Pamplona, Navarrra el 5 de octubre de 2015.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
(CIB) Comunicaciones congresos
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