Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.

<h4>Background</h4>Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aber...

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Autores principales: Beatrice Cousin, Emmanuel Ravet, Sandrine Poglio, Fabienne De Toni, Mélanie Bertuzzi, Hubert Lulka, Ismahane Touil, Mireille André, Jean-Louis Grolleau, Jean-Marie Péron, Jean-Pierre Chavoin, Philippe Bourin, Luc Pénicaud, Louis Casteilla, Louis Buscail, Pierre Cordelier
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spelling oai:doaj.org-article:a8968b24bd9e406a90cb2cd14e9c4f772021-11-25T06:21:34ZAdult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.1932-620310.1371/journal.pone.0006278https://doaj.org/article/a8968b24bd9e406a90cb2cd14e9c4f772009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19609435/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation.<h4>Principal findings</h4>Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth.<h4>Conclusion</h4>These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.Beatrice CousinEmmanuel RavetSandrine PoglioFabienne De ToniMélanie BertuzziHubert LulkaIsmahane TouilMireille AndréJean-Louis GrolleauJean-Marie PéronJean-Pierre ChavoinPhilippe BourinLuc PénicaudLouis CasteillaLouis BuscailPierre CordelierPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 7, p e6278 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Beatrice Cousin
Emmanuel Ravet
Sandrine Poglio
Fabienne De Toni
Mélanie Bertuzzi
Hubert Lulka
Ismahane Touil
Mireille André
Jean-Louis Grolleau
Jean-Marie Péron
Jean-Pierre Chavoin
Philippe Bourin
Luc Pénicaud
Louis Casteilla
Louis Buscail
Pierre Cordelier
Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
description <h4>Background</h4>Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation.<h4>Principal findings</h4>Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth.<h4>Conclusion</h4>These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.
format article
author Beatrice Cousin
Emmanuel Ravet
Sandrine Poglio
Fabienne De Toni
Mélanie Bertuzzi
Hubert Lulka
Ismahane Touil
Mireille André
Jean-Louis Grolleau
Jean-Marie Péron
Jean-Pierre Chavoin
Philippe Bourin
Luc Pénicaud
Louis Casteilla
Louis Buscail
Pierre Cordelier
author_facet Beatrice Cousin
Emmanuel Ravet
Sandrine Poglio
Fabienne De Toni
Mélanie Bertuzzi
Hubert Lulka
Ismahane Touil
Mireille André
Jean-Louis Grolleau
Jean-Marie Péron
Jean-Pierre Chavoin
Philippe Bourin
Luc Pénicaud
Louis Casteilla
Louis Buscail
Pierre Cordelier
author_sort Beatrice Cousin
title Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
title_short Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
title_full Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
title_fullStr Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
title_full_unstemmed Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
title_sort adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/a8968b24bd9e406a90cb2cd14e9c4f77
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