Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.

An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issu...

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Autores principales:	Luisa Salvatori, Francesca Caporuscio, Alessandra Verdina, Giuseppe Starace, Stefania Crispi, Maria Rita Nicotra, Andrea Russo, Raffaele Adolfo Calogero, Emanuela Morgante, Pier Giorgio Natali, Matteo Antonio Russo, Elisa Petrangeli
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e9f619025af45869b36cbbb61c84d80
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spelling	oai:doaj.org-article:2e9f619025af45869b36cbbb61c84d802021-11-18T07:28:49ZCell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.1932-620310.1371/journal.pone.0031467https://doaj.org/article/2e9f619025af45869b36cbbb61c84d802012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22328933/?tool=EBIhttps://doaj.org/toc/1932-6203An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44(+)CD24(-) phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications.Luisa SalvatoriFrancesca CaporuscioAlessandra VerdinaGiuseppe StaraceStefania CrispiMaria Rita NicotraAndrea RussoRaffaele Adolfo CalogeroEmanuela MorgantePier Giorgio NataliMatteo Antonio RussoElisa PetrangeliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31467 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luisa Salvatori Francesca Caporuscio Alessandra Verdina Giuseppe Starace Stefania Crispi Maria Rita Nicotra Andrea Russo Raffaele Adolfo Calogero Emanuela Morgante Pier Giorgio Natali Matteo Antonio Russo Elisa Petrangeli Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
description	An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44(+)CD24(-) phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications.
format	article
author	Luisa Salvatori Francesca Caporuscio Alessandra Verdina Giuseppe Starace Stefania Crispi Maria Rita Nicotra Andrea Russo Raffaele Adolfo Calogero Emanuela Morgante Pier Giorgio Natali Matteo Antonio Russo Elisa Petrangeli
author_facet	Luisa Salvatori Francesca Caporuscio Alessandra Verdina Giuseppe Starace Stefania Crispi Maria Rita Nicotra Andrea Russo Raffaele Adolfo Calogero Emanuela Morgante Pier Giorgio Natali Matteo Antonio Russo Elisa Petrangeli
author_sort	Luisa Salvatori
title	Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
title_short	Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
title_full	Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
title_fullStr	Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
title_full_unstemmed	Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
title_sort	cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2e9f619025af45869b36cbbb61c84d80
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Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors.

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