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Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

INTRODUCTION: Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects asso...

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Autores principales: Das Roy, Lopamudra, Pathangey, Latha B, Tinder, Teresa L, Schettini, Jorge L, Gruber, Helen E, Mukherjee, Pinku
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750117/
https://www.ncbi.nlm.nih.gov/pubmed/19643025
http://dx.doi.org/10.1186/bcr2345
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author Das Roy, Lopamudra
Pathangey, Latha B
Tinder, Teresa L
Schettini, Jorge L
Gruber, Helen E
Mukherjee, Pinku
author_facet Das Roy, Lopamudra
Pathangey, Latha B
Tinder, Teresa L
Schettini, Jorge L
Gruber, Helen E
Mukherjee, Pinku
author_sort Das Roy, Lopamudra
collection PubMed
description INTRODUCTION: Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. METHODS: To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. RESULTS: We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute to the increased metastasis. Treatment with anti-IL17 + celecoxib, an anti-inflammatory drug completely abrogated the development of metastasis and significantly reduced the primary tumor burden. CONCLUSIONS: The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options.
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spelling pubmed-27501172009-09-25 Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis Das Roy, Lopamudra Pathangey, Latha B Tinder, Teresa L Schettini, Jorge L Gruber, Helen E Mukherjee, Pinku Breast Cancer Res Research Article INTRODUCTION: Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. METHODS: To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. RESULTS: We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute to the increased metastasis. Treatment with anti-IL17 + celecoxib, an anti-inflammatory drug completely abrogated the development of metastasis and significantly reduced the primary tumor burden. CONCLUSIONS: The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options. BioMed Central 2009 2009-07-30 /pmc/articles/PMC2750117/ /pubmed/19643025 http://dx.doi.org/10.1186/bcr2345 Text en Copyright © 2009 Das Roy et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Das Roy, Lopamudra
Pathangey, Latha B
Tinder, Teresa L
Schettini, Jorge L
Gruber, Helen E
Mukherjee, Pinku
Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title_full Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title_fullStr Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title_full_unstemmed Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title_short Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
title_sort breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2750117/
https://www.ncbi.nlm.nih.gov/pubmed/19643025
http://dx.doi.org/10.1186/bcr2345
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