Browsing by Author "Sotomayor, Paula C."

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    Dietary Fructose Promotes Prostate Cancer Growth
    (2021) Carreno, Daniela, V; Corro, Nestor B.; Cerda-Infante, Javier F.; Echeverria, Carolina E.; Asencio-Barria, Catalina A.; Torres-Estay, Veronica A.; Mayorga-Weber, Gonzalo A.; Rojas, Pablo A.; Veliz, Loreto P.; Cisternas, Pedro A.; Montecinos, Viviana P.; San Francisco, Ignacio F.; Varas-Godoy, Manuel A.; Sotomayor, Paula C.; Castro, Maite A.; Nualart, Francisco J.; Inestrosa, Nibaldo C.; Godoy, Alejandro S.
    Clinical localization of primary tumors and sites of metastasis by PET is based on the enhanced cellular uptake of 2-deoxy-2-[F-18]-fluoro-D-glucose (FDG). In prostate cancer, however, PET-FDG imaging has shown limited clinical applicability, suggesting that prostate cancer cells may utilize hexoses other than glucose, such as fructose, as the preferred energy source. Our previous studies suggested that prostate cancer cells overexpress fructose transporters, but not glucose transporters, compared with benign cells. Here, we focused on validating the functional expression of fructose transporters and determining whether fructose can modulate the biology of prostate cancer cells in vitro and in vivo. Fructose transporters, Glut5 and Glut9, were significantly upregulated in clinical specimens of prostate cancer when compared with their benign counterparts. Fructose levels in the serum of patients with prostate cancer were significantly higher than healthy subjects. Functional expression of fructose transporters was confirmed in prostate cancer cell lines. A detailed kinetic characterization indicated that Glut5 represents the main functional contributor in mediating fructose transport in prostate cancer cells. Fructose stimulated proliferation and invasion of prostate cancer cells in vitro. In addition, dietary fructose increased the growth of prostate cancer cell line-derived xenograft tumors and promoted prostate cancer cell proliferation in patient- derived xenografts. Gene set enrichment analysis confirmed that fructose stimulation enriched for proliferation-related pathways in prostate cancer cells. These results demonstrate that fructose promotes prostate cancer cell growth and aggressiveness in vitro and in vivo and may represent an alternative energy source for prostate cancer cells.
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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.