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The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well estab...

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Autores principales: Guérard, Adrien, Laurent, Victor, Fromont, Gaëlle, Estève, David, Gilhodes, Julia, Bonnelye, Edith, Le Gonidec, Sophie, Valet, Philippe, Malavaud, Bernard, Reina, Nicolas, Attané, Camille, Muller, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922974/
https://www.ncbi.nlm.nih.gov/pubmed/33671469
http://dx.doi.org/10.3390/ijms22041994
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author Guérard, Adrien
Laurent, Victor
Fromont, Gaëlle
Estève, David
Gilhodes, Julia
Bonnelye, Edith
Le Gonidec, Sophie
Valet, Philippe
Malavaud, Bernard
Reina, Nicolas
Attané, Camille
Muller, Catherine
author_facet Guérard, Adrien
Laurent, Victor
Fromont, Gaëlle
Estève, David
Gilhodes, Julia
Bonnelye, Edith
Le Gonidec, Sophie
Valet, Philippe
Malavaud, Bernard
Reina, Nicolas
Attané, Camille
Muller, Catherine
author_sort Guérard, Adrien
collection PubMed
description Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated.
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spelling pubmed-79229742021-03-03 The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes Guérard, Adrien Laurent, Victor Fromont, Gaëlle Estève, David Gilhodes, Julia Bonnelye, Edith Le Gonidec, Sophie Valet, Philippe Malavaud, Bernard Reina, Nicolas Attané, Camille Muller, Catherine Int J Mol Sci Article Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated. MDPI 2021-02-17 /pmc/articles/PMC7922974/ /pubmed/33671469 http://dx.doi.org/10.3390/ijms22041994 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guérard, Adrien
Laurent, Victor
Fromont, Gaëlle
Estève, David
Gilhodes, Julia
Bonnelye, Edith
Le Gonidec, Sophie
Valet, Philippe
Malavaud, Bernard
Reina, Nicolas
Attané, Camille
Muller, Catherine
The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title_full The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title_fullStr The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title_full_unstemmed The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title_short The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes
title_sort chemokine receptor ccr3 is potentially involved in the homing of prostate cancer cells to bone: implication of bone-marrow adipocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922974/
https://www.ncbi.nlm.nih.gov/pubmed/33671469
http://dx.doi.org/10.3390/ijms22041994
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