CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.

Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorect...

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Autores principales:	Béatrice Cambien, Peggy Richard-Fiardo, Babou F Karimdjee, Violette Martini, Bernard Ferrua, Bruno Pitard, Heidy Schmid-Antomarchi, Annie Schmid-Alliana
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/331ae96239844c2e8fef57a3574437c4
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spelling	oai:doaj.org-article:331ae96239844c2e8fef57a3574437c42021-11-18T07:31:49ZCCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.1932-620310.1371/journal.pone.0028842https://doaj.org/article/331ae96239844c2e8fef57a3574437c42011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22205974/?tool=EBIhttps://doaj.org/toc/1932-6203Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorectal carcinoma clinical specimens and found CCL5 and its receptors over-expressed within primary as well as liver and pulmonary metastases of patients compared to healthy tissues. In vitro, CCL5 increased the growth and migratory responses of colon cancer cells from both human and mouse origins. In addition, systemic treatment of mice with CCL5-directed antibodies reduced the extent of development of subcutaneous colon tumors, of liver metastases and of peritoneal carcinosis. Consistently, we found increased numbers of CD45-immunoreactive cells within the stroma of the remaining lesions as well as at the interface with the healthy tissue. In contrast, selective targeting of CCR5 through administration of TAK-779, a CCR5 antagonist, only partially compromised colon cancer progression. Furthermore, CCL5 neutralization rendered the tumors more sensitive to a PDGFRβ-directed strategy in mice, this combination regimen offering the greatest protection against liver metastases and suppressing macroscopic peritoneal carcinosis. Collectively, our data demonstrate the involvement of CCL5 in the pathogenesis of colorectal carcinoma and point to its potential value as a therapeutic target.Béatrice CambienPeggy Richard-FiardoBabou F KarimdjeeViolette MartiniBernard FerruaBruno PitardHeidy Schmid-AntomarchiAnnie Schmid-AllianaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28842 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Béatrice Cambien Peggy Richard-Fiardo Babou F Karimdjee Violette Martini Bernard Ferrua Bruno Pitard Heidy Schmid-Antomarchi Annie Schmid-Alliana CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
description	Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorectal carcinoma clinical specimens and found CCL5 and its receptors over-expressed within primary as well as liver and pulmonary metastases of patients compared to healthy tissues. In vitro, CCL5 increased the growth and migratory responses of colon cancer cells from both human and mouse origins. In addition, systemic treatment of mice with CCL5-directed antibodies reduced the extent of development of subcutaneous colon tumors, of liver metastases and of peritoneal carcinosis. Consistently, we found increased numbers of CD45-immunoreactive cells within the stroma of the remaining lesions as well as at the interface with the healthy tissue. In contrast, selective targeting of CCR5 through administration of TAK-779, a CCR5 antagonist, only partially compromised colon cancer progression. Furthermore, CCL5 neutralization rendered the tumors more sensitive to a PDGFRβ-directed strategy in mice, this combination regimen offering the greatest protection against liver metastases and suppressing macroscopic peritoneal carcinosis. Collectively, our data demonstrate the involvement of CCL5 in the pathogenesis of colorectal carcinoma and point to its potential value as a therapeutic target.
format	article
author	Béatrice Cambien Peggy Richard-Fiardo Babou F Karimdjee Violette Martini Bernard Ferrua Bruno Pitard Heidy Schmid-Antomarchi Annie Schmid-Alliana
author_facet	Béatrice Cambien Peggy Richard-Fiardo Babou F Karimdjee Violette Martini Bernard Ferrua Bruno Pitard Heidy Schmid-Antomarchi Annie Schmid-Alliana
author_sort	Béatrice Cambien
title	CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
title_short	CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
title_full	CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
title_fullStr	CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
title_full_unstemmed	CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.
title_sort	ccl5 neutralization restricts cancer growth and potentiates the targeting of pdgfrβ in colorectal carcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/331ae96239844c2e8fef57a3574437c4
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CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.

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