Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium

Abstract Aggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted b...

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Autores principales:	Fei Su, Alexes C. Daquinag, Songyeon Ahn, Achinto Saha, Yulin Dai, Zhongming Zhao, John DiGiovanni, Mikhail G. Kolonin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/278639b602984827ab52b214507bb321
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spelling	oai:doaj.org-article:278639b602984827ab52b214507bb3212021-12-02T16:36:09ZProgression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium10.1038/s41698-021-00160-92397-768Xhttps://doaj.org/article/278639b602984827ab52b214507bb3212021-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00160-9https://doaj.org/toc/2397-768XAbstract Aggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted by obesity and suppressed upon pharmacological ASC depletion in HiMyc mice, a spontaneous genetic model of prostate cancer. CXCL12 expression in tumors was associated with ASC recruitment and localized to stromal cells expressing platelet-derived growth factor receptors Pdgfra and Pdgfrb. The role of this chemokine secreted by stromal cells in cancer progression was further investigated by using tissue-specific knockout models. ASC deletion of CXCL12 gene in the Pdgfr + lineages suppressed tumor growth and EMT, indicating stroma as the key source of CXCL12. Clinical sample analysis revealed that CXCL12 expression by peritumoral adipose stroma is increased in obesity, and that the correlating increase in Pdgfr/CXCL12 expression in the tumor is linked with decreased survival of patients with prostate carcinoma. Our study establishes ASC as the source of CXCL12 driving tumor aggressiveness and outlines an approach to treatment of carcinoma progression.Fei SuAlexes C. DaquinagSongyeon AhnAchinto SahaYulin DaiZhongming ZhaoJohn DiGiovanniMikhail G. KoloninNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Fei Su Alexes C. Daquinag Songyeon Ahn Achinto Saha Yulin Dai Zhongming Zhao John DiGiovanni Mikhail G. Kolonin Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
description	Abstract Aggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted by obesity and suppressed upon pharmacological ASC depletion in HiMyc mice, a spontaneous genetic model of prostate cancer. CXCL12 expression in tumors was associated with ASC recruitment and localized to stromal cells expressing platelet-derived growth factor receptors Pdgfra and Pdgfrb. The role of this chemokine secreted by stromal cells in cancer progression was further investigated by using tissue-specific knockout models. ASC deletion of CXCL12 gene in the Pdgfr + lineages suppressed tumor growth and EMT, indicating stroma as the key source of CXCL12. Clinical sample analysis revealed that CXCL12 expression by peritumoral adipose stroma is increased in obesity, and that the correlating increase in Pdgfr/CXCL12 expression in the tumor is linked with decreased survival of patients with prostate carcinoma. Our study establishes ASC as the source of CXCL12 driving tumor aggressiveness and outlines an approach to treatment of carcinoma progression.
format	article
author	Fei Su Alexes C. Daquinag Songyeon Ahn Achinto Saha Yulin Dai Zhongming Zhao John DiGiovanni Mikhail G. Kolonin
author_facet	Fei Su Alexes C. Daquinag Songyeon Ahn Achinto Saha Yulin Dai Zhongming Zhao John DiGiovanni Mikhail G. Kolonin
author_sort	Fei Su
title	Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
title_short	Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
title_full	Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
title_fullStr	Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
title_full_unstemmed	Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium
title_sort	progression of prostate carcinoma is promoted by adipose stromal cell-secreted cxcl12 signaling in prostate epithelium
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/278639b602984827ab52b214507bb321
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Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium

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