Heme oxygenase-1 in macrophages controls prostate cancer progression

Zsuzsanna Nemeth; Mailin Li; Eva Csizmadia; Balazs Döme; Martin Johansson; Jenny Liao Persson; Pankaj Seth; Leo Otterbein; Barbara Wegiel

doi:10.18632/oncotarget.5284

Heme oxygenase-1 in macrophages controls prostate cancer progression

Zsuzsanna Nemeth, Mailin Li, Eva Csizmadia, Balazs Döme, Martin Johansson, Jenny Liao Persson, Pankaj Seth, Leo Otterbein, Barbara Wegiel

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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.

Original language	English
Pages (from-to)	33675-88
Number of pages	14
Journal	Oncotarget
Volume	6
Issue number	32
DOIs	https://doi.org/10.18632/oncotarget.5284
Publication status	Published - 16 Oct 2015
Externally published	Yes

Keywords

Animals
Cadherins
Cell Line, Tumor
Cell Proliferation
Disease Progression
Heme Oxygenase-1
Heterografts
Humans
Macrophages
Male
Membrane Proteins
Mice
Mice, Knockout
Prostatic Neoplasms
Tumor Microenvironment
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.5284Licence: CC BY

Heme oxygenase-1 in macrophages controls prostate cancer progression
Copyright 2015 The Authors This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 4.67 MBLicence: CC BY

Cite this

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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.",

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author = "Zsuzsanna Nemeth and Mailin Li and Eva Csizmadia and Balazs D{\"o}me and Martin Johansson and Persson, {Jenny Liao} and Pankaj Seth and Leo Otterbein and Barbara Wegiel",

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doi = "10.18632/oncotarget.5284",

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AU - Nemeth, Zsuzsanna

AU - Li, Mailin

AU - Csizmadia, Eva

AU - Döme, Balazs

AU - Johansson, Martin

AU - Persson, Jenny Liao

AU - Seth, Pankaj

AU - Otterbein, Leo

AU - Wegiel, Barbara

PY - 2015/10/16

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N2 - 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.

AB - 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.

KW - Animals

KW - Cadherins

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Disease Progression

KW - Heme Oxygenase-1

KW - Heterografts

KW - Humans

KW - Macrophages

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mice, Knockout

KW - Prostatic Neoplasms

KW - Tumor Microenvironment

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

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DO - 10.18632/oncotarget.5284

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SN - 1949-2553

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SP - 33675

EP - 33688

JO - Oncotarget

JF - Oncotarget

IS - 32

ER -

Heme oxygenase-1 in macrophages controls prostate cancer progression

Abstract

Keywords

UN SDGs

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