Role of stromal activin A in human pancreatic cancer and metastasis in mice

Abstract Pancreatic ductal adenocarcinoma (PDAC) has extensive stromal involvement and remains one of the cancers with the highest mortality rates. Activin A has been implicated in colon cancer and its stroma but its role in the stroma of PDAC has not been elucidated. Activin A expression in cancer...

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Autores principales:	Georgina Mancinelli, Carolina Torres, Nancy Krett, Jessica Bauer, Karla Castellanos, Ron McKinney, David Dawson, Grace Guzman, Rosa Hwang, Sam Grimaldo, Paul Grippo, Barbara Jung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83e0be2dcf7e423bbd2aa5ad936461d6
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spelling	oai:doaj.org-article:83e0be2dcf7e423bbd2aa5ad936461d62021-12-02T14:27:46ZRole of stromal activin A in human pancreatic cancer and metastasis in mice10.1038/s41598-021-87213-y2045-2322https://doaj.org/article/83e0be2dcf7e423bbd2aa5ad936461d62021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87213-yhttps://doaj.org/toc/2045-2322Abstract Pancreatic ductal adenocarcinoma (PDAC) has extensive stromal involvement and remains one of the cancers with the highest mortality rates. Activin A has been implicated in colon cancer and its stroma but its role in the stroma of PDAC has not been elucidated. Activin A expression in cancer and stroma was assessed in human PDAC tissue microarrays (TMA). Activin A expression in human TMA is significantly higher in cancer samples, with expression in stroma correlated with shorter survival. Cultured pancreatic stellate cells (PSC) were found to secrete high levels of activin A resulting in PDAC cell migration that is abolished by anti-activin A neutralizing antibody. KPC mice treated with anti-activin A neutralizing antibody were evaluated for tumors, lesions and metastases quantified by immunohistochemistry. KPC mice with increased tumor burden express high plasma activin A. Treating KPC mice with an activin A neutralizing antibody does not reduce primary tumor size but decreases tumor metastases. From these data we conclude that PDAC patients with high activin A expression in stroma have a worse prognosis. PSCs secrete activin A, promoting increased PDAC migration. Inhibition of activin A in mice decreased metastases. Hence, stroma-rich PDAC patients might benefit from activin A inhibition.Georgina MancinelliCarolina TorresNancy KrettJessica BauerKarla CastellanosRon McKinneyDavid DawsonGrace GuzmanRosa HwangSam GrimaldoPaul GrippoBarbara JungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Georgina Mancinelli Carolina Torres Nancy Krett Jessica Bauer Karla Castellanos Ron McKinney David Dawson Grace Guzman Rosa Hwang Sam Grimaldo Paul Grippo Barbara Jung Role of stromal activin A in human pancreatic cancer and metastasis in mice
description	Abstract Pancreatic ductal adenocarcinoma (PDAC) has extensive stromal involvement and remains one of the cancers with the highest mortality rates. Activin A has been implicated in colon cancer and its stroma but its role in the stroma of PDAC has not been elucidated. Activin A expression in cancer and stroma was assessed in human PDAC tissue microarrays (TMA). Activin A expression in human TMA is significantly higher in cancer samples, with expression in stroma correlated with shorter survival. Cultured pancreatic stellate cells (PSC) were found to secrete high levels of activin A resulting in PDAC cell migration that is abolished by anti-activin A neutralizing antibody. KPC mice treated with anti-activin A neutralizing antibody were evaluated for tumors, lesions and metastases quantified by immunohistochemistry. KPC mice with increased tumor burden express high plasma activin A. Treating KPC mice with an activin A neutralizing antibody does not reduce primary tumor size but decreases tumor metastases. From these data we conclude that PDAC patients with high activin A expression in stroma have a worse prognosis. PSCs secrete activin A, promoting increased PDAC migration. Inhibition of activin A in mice decreased metastases. Hence, stroma-rich PDAC patients might benefit from activin A inhibition.
format	article
author	Georgina Mancinelli Carolina Torres Nancy Krett Jessica Bauer Karla Castellanos Ron McKinney David Dawson Grace Guzman Rosa Hwang Sam Grimaldo Paul Grippo Barbara Jung
author_facet	Georgina Mancinelli Carolina Torres Nancy Krett Jessica Bauer Karla Castellanos Ron McKinney David Dawson Grace Guzman Rosa Hwang Sam Grimaldo Paul Grippo Barbara Jung
author_sort	Georgina Mancinelli
title	Role of stromal activin A in human pancreatic cancer and metastasis in mice
title_short	Role of stromal activin A in human pancreatic cancer and metastasis in mice
title_full	Role of stromal activin A in human pancreatic cancer and metastasis in mice
title_fullStr	Role of stromal activin A in human pancreatic cancer and metastasis in mice
title_full_unstemmed	Role of stromal activin A in human pancreatic cancer and metastasis in mice
title_sort	role of stromal activin a in human pancreatic cancer and metastasis in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/83e0be2dcf7e423bbd2aa5ad936461d6
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Role of stromal activin A in human pancreatic cancer and metastasis in mice

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