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A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model
Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078077/ https://www.ncbi.nlm.nih.gov/pubmed/27105499 http://dx.doi.org/10.18632/oncotarget.8859 |
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author | Msaki, Aichi Pastò, Anna Curtarello, Matteo Arigoni, Maddalena Barutello, Giuseppina Calogero, Raffaele Adolfo Macagno, Marco Cavallo, Federica Amadori, Alberto Indraccolo, Stefano |
author_facet | Msaki, Aichi Pastò, Anna Curtarello, Matteo Arigoni, Maddalena Barutello, Giuseppina Calogero, Raffaele Adolfo Macagno, Marco Cavallo, Federica Amadori, Alberto Indraccolo, Stefano |
author_sort | Msaki, Aichi |
collection | PubMed |
description | Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment. |
format | Online Article Text |
id | pubmed-5078077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50780772016-10-28 A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model Msaki, Aichi Pastò, Anna Curtarello, Matteo Arigoni, Maddalena Barutello, Giuseppina Calogero, Raffaele Adolfo Macagno, Marco Cavallo, Federica Amadori, Alberto Indraccolo, Stefano Oncotarget Research Paper Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment. Impact Journals LLC 2016-04-20 /pmc/articles/PMC5078077/ /pubmed/27105499 http://dx.doi.org/10.18632/oncotarget.8859 Text en Copyright: © 2016 Msaki et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Msaki, Aichi Pastò, Anna Curtarello, Matteo Arigoni, Maddalena Barutello, Giuseppina Calogero, Raffaele Adolfo Macagno, Marco Cavallo, Federica Amadori, Alberto Indraccolo, Stefano A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title | A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title_full | A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title_fullStr | A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title_full_unstemmed | A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title_short | A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model |
title_sort | hypoxic signature marks tumors formed by disseminated tumor cells in the balb-neut mammary cancer model |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078077/ https://www.ncbi.nlm.nih.gov/pubmed/27105499 http://dx.doi.org/10.18632/oncotarget.8859 |
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