The Differential Paracrine Role of the Endothelium in Prostate Cancer Cells

Verónica Torres-Estay, Michalis Mastri, Spencer Rosario, Patricia Fuenzalida, Carolina E. Echeverría, Emilia Flores, Anica Watts, Javier Cerda-Infante, Viviana P. Montecinos, Paula C. Sotomayor, Julio Amigo, Carlos Escudero, Francisco Nualart, John M.L. Ebos, Dominic J. Smiraglia, Alejandro S. Godoy*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations

    Abstract

    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.

    Original languageEnglish
    Article number4750
    Pages (from-to)4750
    JournalCancers
    Volume14
    Issue number19
    DOIs
    StatePublished - Oct 2022

    Bibliographical note

    Publisher Copyright:
    © 2022 by the authors.

    Keywords

    • angiocrine effect
    • cancer
    • endothelial cells
    • microenvironment
    • prostate cancer

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