In Vivo Hemin Conditioning Targets the Vascular and Immunologic Compartments and Restrains Prostate Tumor Development

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Felipe M JaworskiElba Vazquez

Abstract

Purpose: Conditioning strategies constitute a relatively unexplored and exciting opportunity to shape tumor fate by targeting the tumor microenvironment. In this study, we assessed how hemin, a pharmacologic inducer of heme oxygenase-1 (HO-1), has an impact on prostate cancer development in an in vivo conditioning model.Experimental Design: The stroma of C57BL/6 mice was conditioned by subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge. Complementary in vitro and in vivo assays were performed to evaluate hemin effect on both angiogenesis and the immune response. To gain clinical insight, we used prostate cancer patient-derived samples in our studies to assess the expression of HO-1 and other relevant genes.Results: Conditioning resulted in increased tumor latency and decreased initial growth rate. Histologic analysis of tumors grown in conditioned mice revealed impaired vascularization. Hemin-treated human umbilical vein endothelial cells (HUVEC) exhibited decreased tubulogenesis in vitro only in the presence of TRAMP-C1-conditioned media. Subcutaneous hemin conditioning hindered tumor-associated neovascularization in an in vivo Matrigel plug assay. In addition, hemin boosted CD8(+) T-cell proliferation and ...Continue Reading

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Citations

Jun 4, 2019·International Journal of Molecular Sciences·Zsombor Melegh, Sebastian Oltean
Apr 18, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanwei WuWei Tang
Mar 1, 2019·International Journal of Molecular Sciences·Daiana B LeonardiJavier Cotignola
Oct 16, 2018·Frontiers in Immunology·Enrique CorapiDiego Laderach
Apr 25, 2019·Nature Reviews. Urology·Neus Martínez-BoschPilar Navarro
Dec 10, 2020·Journal for Immunotherapy of Cancer·Carolina TiraboschiDaniel Compagno
Jul 3, 2021·Antioxidants·Florencia CascardoJavier Cotignola

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