title: Heme oxygenase-1 in macrophages controls prostate cancer progression.
abstract: Innate immune cells strongly influence cancer growth and progression via multiple mechanisms including regulation of epithelial to mesenchymal transition (EMT). In this study, we investigated whether expression of the metabolic gene, heme oxygenase-1 (HO-1) in tumor microenvironment imparts significant effects on prostate cancer progression.We showed that HO-1 is expressed in MARCO-positive macrophages in prostate cancer (PCa) xenografts and human prostate cancers. We demonstrated that macrophage specific (LyzM-Cre) conditional deletion of HO-1 suppressed growth of PC3 xenografts in vivo and delayed progression of prostate intraepithelial neoplasia (PIN) in TRAMP mice. However, initiation and progression of cancer xenografts in the presence of macrophages lacking HO-1 resulted in loss of E-cadherin, a known marker of poor prognosis as well as EMT. Application of CO, a product of HO-1 catalysis, increased levels of E-cadherin in the adherens junctions between cancer cells. We further showed that HO-1-driven expression of E-cadherin in cancer cells cultured in the presence of macrophages is dependent on mitochondrial activity of cancer cells.In summary, these data suggest that HO-1-derived CO from tumor-associated macrophages influences, in part, E-cadherin expression and thus tumor initiation and progression.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Department of Tumor Biology, National Koranyi Institute of TB and Pulmonology, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Nemeth
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Mailin
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Csizmadia
authors.affiliation: Department of Tumor Biology, National Koranyi Institute of TB and Pulmonology, Budapest, Hungary.|Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.|Department of Thoracic Surgery, National Institute of Oncology, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Döme
authors.affiliation: Department of Laboratory Medicine, Lund University, Malmo, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Laboratory Medicine, Lund University, Malmo, Sweden.
authors.forename: Jenny Liao
authors.initials: JL
authors.lastname: Persson
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Otterbein
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wegiel
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: E-cadherin; heme oxygenase-1; mitochondria; tumor microenvironment; tumor-associated macrophages