Cargando…

T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer

Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenv...

Descripción completa

Detalles Bibliográficos
Autores principales: Monteiro, Ana Carolina, Leal, Ana Carolina, Gonçalves-Silva, Triciana, Mercadante, Ana Carolina T., Kestelman, Fabiola, Chaves, Sacha Braun, Azevedo, Ricardo Bentes, Monteiro, João P., Bonomo, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730734/
https://www.ncbi.nlm.nih.gov/pubmed/23935856
http://dx.doi.org/10.1371/journal.pone.0068171
_version_ 1782279105901756416
author Monteiro, Ana Carolina
Leal, Ana Carolina
Gonçalves-Silva, Triciana
Mercadante, Ana Carolina T.
Kestelman, Fabiola
Chaves, Sacha Braun
Azevedo, Ricardo Bentes
Monteiro, João P.
Bonomo, Adriana
author_facet Monteiro, Ana Carolina
Leal, Ana Carolina
Gonçalves-Silva, Triciana
Mercadante, Ana Carolina T.
Kestelman, Fabiola
Chaves, Sacha Braun
Azevedo, Ricardo Bentes
Monteiro, João P.
Bonomo, Adriana
author_sort Monteiro, Ana Carolina
collection PubMed
description Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenvironment, the pre-metastatic niche, for the establishment of the metastatic foci. In bone metastatic niche, metastatic cells stimulate bone consumption resulting in the release of growth factors that feed the tumor, establishing a vicious cycle between the bone remodeling system and the tumor itself. Yet, how the pre-metastatic niches arise in the bone tissue remains unclear. Here we show that tumor-specific T cells induce osteolytic bone disease before bone colonization. T cells pro-metastatic activity correlate with a pro-osteoclastogenic cytokine profile, including RANKL, a master regulator of osteoclastogenesis. In vivo inhibition of RANKL from tumor-specific T cells completely blocks bone loss and metastasis. Our results unveil an unexpected role for RANKL-derived from T cells in setting the pre-metastatic niche and promoting tumor spread. We believe this information can bring new possibilities for the development of prognostic and therapeutic tools based on modulation of T cell activity for prevention and treatment of bone metastasis.
format Online
Article
Text
id pubmed-3730734
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37307342013-08-09 T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer Monteiro, Ana Carolina Leal, Ana Carolina Gonçalves-Silva, Triciana Mercadante, Ana Carolina T. Kestelman, Fabiola Chaves, Sacha Braun Azevedo, Ricardo Bentes Monteiro, João P. Bonomo, Adriana PLoS One Research Article Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenvironment, the pre-metastatic niche, for the establishment of the metastatic foci. In bone metastatic niche, metastatic cells stimulate bone consumption resulting in the release of growth factors that feed the tumor, establishing a vicious cycle between the bone remodeling system and the tumor itself. Yet, how the pre-metastatic niches arise in the bone tissue remains unclear. Here we show that tumor-specific T cells induce osteolytic bone disease before bone colonization. T cells pro-metastatic activity correlate with a pro-osteoclastogenic cytokine profile, including RANKL, a master regulator of osteoclastogenesis. In vivo inhibition of RANKL from tumor-specific T cells completely blocks bone loss and metastasis. Our results unveil an unexpected role for RANKL-derived from T cells in setting the pre-metastatic niche and promoting tumor spread. We believe this information can bring new possibilities for the development of prognostic and therapeutic tools based on modulation of T cell activity for prevention and treatment of bone metastasis. Public Library of Science 2013-07-18 /pmc/articles/PMC3730734/ /pubmed/23935856 http://dx.doi.org/10.1371/journal.pone.0068171 Text en © 2013 Monteiro et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Monteiro, Ana Carolina
Leal, Ana Carolina
Gonçalves-Silva, Triciana
Mercadante, Ana Carolina T.
Kestelman, Fabiola
Chaves, Sacha Braun
Azevedo, Ricardo Bentes
Monteiro, João P.
Bonomo, Adriana
T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title_full T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title_fullStr T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title_full_unstemmed T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title_short T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
title_sort t cells induce pre-metastatic osteolytic disease and help bone metastases establishment in a mouse model of metastatic breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730734/
https://www.ncbi.nlm.nih.gov/pubmed/23935856
http://dx.doi.org/10.1371/journal.pone.0068171
work_keys_str_mv AT monteiroanacarolina tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT lealanacarolina tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT goncalvessilvatriciana tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT mercadanteanacarolinat tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT kestelmanfabiola tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT chavessachabraun tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT azevedoricardobentes tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT monteirojoaop tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer
AT bonomoadriana tcellsinducepremetastaticosteolyticdiseaseandhelpbonemetastasesestablishmentinamousemodelofmetastaticbreastcancer