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Heme oxygenase-1 in macrophages controls prostate cancer progression.

Nemeth, Zsuzsanna; Li, Mailin; Csizmadia, Eva; Döme, Balazs; Johansson, Martin LU ; Persson, Jenny L LU ; Seth, Pankaj; Otterbein, Leo and Wegiel, Barbara (2015) In Oncotarget 6(32). p.33675-33688
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncotarget
volume
6
issue
32
pages
33675 - 33688
publisher
Impact Journals, LLC
external identifiers
  • pmid:26418896
  • wos:000363186600118
  • scopus:84946017047
ISSN
1949-2553
DOI
10.18632/oncotarget.5284
language
English
LU publication?
yes
id
aa0081e1-2ac1-4c12-8166-f6ed6176602d (old id 8034496)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26418896?dopt=Abstract
date added to LUP
2015-10-03 12:35:42
date last changed
2017-10-01 04:11:15
@article{aa0081e1-2ac1-4c12-8166-f6ed6176602d,
  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.},
  author       = {Nemeth, Zsuzsanna and Li, Mailin and Csizmadia, Eva and Döme, Balazs and Johansson, Martin and Persson, Jenny L and Seth, Pankaj and Otterbein, Leo and Wegiel, Barbara},
  issn         = {1949-2553},
  language     = {eng},
  number       = {32},
  pages        = {33675--33688},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Heme oxygenase-1 in macrophages controls prostate cancer progression.},
  url          = {http://dx.doi.org/10.18632/oncotarget.5284},
  volume       = {6},
  year         = {2015},
}