Browsing by Author "Escudero, Carlos"

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    Adenosine promoted angiogenesis mediated by the release of small extracellular vesicles from human endothelial progenitor cells
    (2023) Oporto, Katherine; Radojkovic, Claudia; Mellisho, Edwin A.; Zuniga, Felipe; Ormazabal, Valeska; Guzman-Gutierrez, Enrique; Nova-Lamperti, Estefania; Rodriguez-Alvarez, Lleretny; Aranda, Mario; Escudero, Carlos; Aguayo, Claudio
    Endothelial progenitor cells (EPCs) are stem cells mainly derived from bone marrow; from where they migrate to repair and regenerate damaged tissues. eEPCs have been classified into two sub-populations, early (eEPC) and late EPCs (lEPC), depending on maturation stages in vitro. In addition, eEPC release endocrine mediators, including small extracellular vesicles (sEVs), which in turn may enhance the eEPC-mediated wound healing properties. Nevertheless, adenosine contributes to angiogenesis by recruiting eEPC at the injury site. However, whether ARs may enhance the secretome of eEPC, including sEVs, is unknown. Therefore, we aimed to inves-tigate whether AR activation increase the release of sEVs in eEPC, which in turn has paracrine effects on recipient endothelial cells. Results shown that 5 '-N-ethylcarboxamidoadenosine (NECA), a non-selective agonist, increase both the protein levels of the vascular endothelial growth factor (VEGF), and the number of sEVs released to the conditioned medium (CM) in primary culture of eEPC. Importantly, CM and EVs harvested from NECA-stimulated eEPC promote in vitro angiogenesis, without changes in cell proliferation, in recipient ECV-304 endothelial cells. This constitutes the first evidence showing that adenosine enhances sEVs release from eEPC, which has pro-angiogenic capacity on recipient endothelial cells.
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    Potential Cell Signalling Mechanisms Involved in Differential Placental Angiogenesis in Mild and Severe Pre-Eclampsia
    (2009) Escudero, Carlos; Westermeier Lafuente, Francisco David; Sobrevía Luarte, Luis Alberto
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    Potential role of A2B adenosine receptors on proliferation/migration of fetal endothelium derived from preeclamptic pregnancies
    (2014) Acurio, Jesenia; Troncoso, Felipe; Bertoglia, Patricio; Salomon, Carlos; Aguayo, Claudio; Sobrevía Luarte, Luis Alberto; Escudero, Carlos
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    The Differential Paracrine Role of the Endothelium in Prostate Cancer Cells
    (2022) Torres-Estay, Veronica; Mastri, Michalis; Rosario, Spencer; Fuenzalida, Patricia; Echeverria, Carolina E.; Flores, Emilia; Watts, Anica; Cerda-Infante, Javier; Montecinos, Viviana P.; Sotomayor, Paula C.; Amigo, Julio; Escudero, Carlos; Nualart, Francisco; Ebos, John M. L.; Smiraglia, Dominic J.; Godoy, Alejandro S.
    Simple Summary A growing body of literature supports the concept that a tumor mass is under the strict control of the microvascular endothelium and that the perfusion of oxygen and nutrients by capillary vessels to the tumor mass is reinforced by potent paracrine activity from the vascular endothelial cells. In our study, we investigate the biological and molecular implications of the paracrine crosstalk between vascular endothelial cells and prostate cancer cells. Our results indicate that the endothelial cells were able to secrete molecular signals that promote the proliferation and growth of low and highly aggressive prostate cancer cells and selectively increased the migration, invasion and metastatic potential of highly aggressive prostate cancer cells. The molecular analyses indicated that endothelial cells induced a differential effect on gene expression profile when comparing low versus highly aggressive prostate cancer cells, causing an enrichment of epigenetic changes in migratory pathways in highly aggressive prostate cancer cells. In conclusion, our results indicate that endothelial cells release signals that favor tumor growth and aggressiveness and that this interaction may play an important role in the progression of prostate cancer. The survival of patients with solid tumors, such as prostate cancer (PCa), has been limited and fleeting with anti-angiogenic therapies. It was previously thought that the mechanism by which the vasculature regulates tumor growth was driven by a passive movement of oxygen and nutrients to the tumor tissue. However, previous evidence suggests that endothelial cells have an alternative role in changing the behavior of tumor cells and contributing to cancer progression. Determining the impact of molecular signals/growth factors released by endothelial cells (ECs) on established PCa cell lines in vitro and in vivo could help to explain the mechanism by which ECs regulate tumor growth. Using cell-conditioned media collected from HUVEC (HUVEC-CM), our data show the stimulated proliferation of all the PCa cell lines tested. However, in more aggressive PCa cell lines, HUVEC-CM selectively promoted migration and invasion in vitro and in vivo. Using a PCa-cell-line-derived xenograft model co-injected with HUVEC or preincubated with HUVEC-CM, our results are consistent with the in vitro data, showing enhanced tumor growth, increased tumor microvasculature and promoted metastasis. Gene set enrichment analyses from RNA-Seq gene expression profiles showed that HUVEC-CM induced a differential effect on gene expression when comparing low versus highly aggressive PCa cell lines, demonstrating epigenetic and migratory pathway enrichments in highly aggressive PCa cells. In summary, paracrine stimulation by HUVEC increased PCa cell proliferation and tumor growth and selectively promoted migration and metastatic potential in more aggressive PCa cell lines.