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Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases

Hemopexin (Hx) is a scavenger of labile heme. Herein, we present data defining the role of tumor stroma-expressed Hx in suppressing cancer progression. Labile heme and Hx levels are inversely correlated in the plasma of patients with prostate cancer (PCa). Further, low expression of Hx in PCa biopsi...

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Autores principales: Canesin, Giacomo, Di Ruscio, Annalisa, Li, Mailin, Ummarino, Simone, Hedblom, Andreas, Choudhury, Reeham, Krzyzanowska, Agnieszka, Csizmadia, Eva, Palominos, Macarena, Stiehm, Anna, Ebralidze, Alexander, Chen, Shao-Yong, Bassal, Mahmoud A., Zhao, Ping, Tolosano, Emanuela, Hurley, Laurence, Bjartell, Anders, Tenen, Daniel G., Wegiel, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551404/
https://www.ncbi.nlm.nih.gov/pubmed/32966797
http://dx.doi.org/10.1016/j.celrep.2020.108181
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author Canesin, Giacomo
Di Ruscio, Annalisa
Li, Mailin
Ummarino, Simone
Hedblom, Andreas
Choudhury, Reeham
Krzyzanowska, Agnieszka
Csizmadia, Eva
Palominos, Macarena
Stiehm, Anna
Ebralidze, Alexander
Chen, Shao-Yong
Bassal, Mahmoud A.
Zhao, Ping
Tolosano, Emanuela
Hurley, Laurence
Bjartell, Anders
Tenen, Daniel G.
Wegiel, Barbara
author_facet Canesin, Giacomo
Di Ruscio, Annalisa
Li, Mailin
Ummarino, Simone
Hedblom, Andreas
Choudhury, Reeham
Krzyzanowska, Agnieszka
Csizmadia, Eva
Palominos, Macarena
Stiehm, Anna
Ebralidze, Alexander
Chen, Shao-Yong
Bassal, Mahmoud A.
Zhao, Ping
Tolosano, Emanuela
Hurley, Laurence
Bjartell, Anders
Tenen, Daniel G.
Wegiel, Barbara
author_sort Canesin, Giacomo
collection PubMed
description Hemopexin (Hx) is a scavenger of labile heme. Herein, we present data defining the role of tumor stroma-expressed Hx in suppressing cancer progression. Labile heme and Hx levels are inversely correlated in the plasma of patients with prostate cancer (PCa). Further, low expression of Hx in PCa biopsies characterizes poorly differentiated tumors and correlates with earlier time to relapse. Significantly, heme promotes tumor growth and metastases in an orthotopic murine model of PCa, with the most aggressive phenotype detected in mice lacking Hx. Mechanistically, labile heme accumulates in the nucleus and modulates specific gene expression via interacting with guanine quadruplex (G4) DNA structures to promote PCa growth. We identify c-MYC as a heme:G4-regulated gene and a major player in heme-driven cancer progression. Collectively, these results reveal that sequestration of labile heme by Hx may block heme-driven tumor growth and metastases, suggesting a potential strategy to prevent and/or arrest cancer dissemination.
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spelling pubmed-75514042020-10-13 Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases Canesin, Giacomo Di Ruscio, Annalisa Li, Mailin Ummarino, Simone Hedblom, Andreas Choudhury, Reeham Krzyzanowska, Agnieszka Csizmadia, Eva Palominos, Macarena Stiehm, Anna Ebralidze, Alexander Chen, Shao-Yong Bassal, Mahmoud A. Zhao, Ping Tolosano, Emanuela Hurley, Laurence Bjartell, Anders Tenen, Daniel G. Wegiel, Barbara Cell Rep Article Hemopexin (Hx) is a scavenger of labile heme. Herein, we present data defining the role of tumor stroma-expressed Hx in suppressing cancer progression. Labile heme and Hx levels are inversely correlated in the plasma of patients with prostate cancer (PCa). Further, low expression of Hx in PCa biopsies characterizes poorly differentiated tumors and correlates with earlier time to relapse. Significantly, heme promotes tumor growth and metastases in an orthotopic murine model of PCa, with the most aggressive phenotype detected in mice lacking Hx. Mechanistically, labile heme accumulates in the nucleus and modulates specific gene expression via interacting with guanine quadruplex (G4) DNA structures to promote PCa growth. We identify c-MYC as a heme:G4-regulated gene and a major player in heme-driven cancer progression. Collectively, these results reveal that sequestration of labile heme by Hx may block heme-driven tumor growth and metastases, suggesting a potential strategy to prevent and/or arrest cancer dissemination. 2020-09-22 /pmc/articles/PMC7551404/ /pubmed/32966797 http://dx.doi.org/10.1016/j.celrep.2020.108181 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Canesin, Giacomo
Di Ruscio, Annalisa
Li, Mailin
Ummarino, Simone
Hedblom, Andreas
Choudhury, Reeham
Krzyzanowska, Agnieszka
Csizmadia, Eva
Palominos, Macarena
Stiehm, Anna
Ebralidze, Alexander
Chen, Shao-Yong
Bassal, Mahmoud A.
Zhao, Ping
Tolosano, Emanuela
Hurley, Laurence
Bjartell, Anders
Tenen, Daniel G.
Wegiel, Barbara
Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title_full Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title_fullStr Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title_full_unstemmed Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title_short Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases
title_sort scavenging of labile heme by hemopexin is a key checkpoint in cancer growth and metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551404/
https://www.ncbi.nlm.nih.gov/pubmed/32966797
http://dx.doi.org/10.1016/j.celrep.2020.108181
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