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peartrout167Lv1
28 Sep 2019
Abstract 1
Breast cancer-associated metastasis is significantly increased ina
model of autoimmune arthritis
Lopamudra Das Roy,1,2 Latha B Pathangey,1 Teresa L Tinder,1,2 JorgeL Schettini,1,2 Helen E Gruber,3 and Pinku Mukherjee1,2
Breast Cancer Res. 2009; 11(4): R56.
Introduction
Sites of chronic inflammation are often associated with theestablishment and growth of various malignancies including breastcancer. A common inflammatory condition in humans is autoimmunearthritis (AA) that causes inflammation and deformity of thejoints. Other systemic effects associated with arthritis includeincreased cellular infiltration and inflammation of the lungs.Several studies have reported statistically significant risk ratiosbetween AA and breast cancer. Despite this knowledge, available fora decade, it has never been questioned if the site of chronicinflammation linked to AA creates a milieu that attracts tumorcells to home and grow in the inflamed bones and lungs which arefrequent sites of breast cancer metastasis.
Methods
To determine if chronic inflammation induced by autoimmunearthritis contributes to increased breast cancer-associatedmetastasis, we generated mammary gland tumors in SKG mice that weregenetically prone to develop AA. Two breast cancer cell lines, onehighly metastatic (4T1) and the other non-metastatic (TUBO) wereused to generate the tumors in the mammary fat pad. Lung and bonemetastasis and the associated inflammatory milieu were evaluated inthe arthritic versus the non-arthritic mice.
Results
We report a three-fold increase in lung metastasis and asignificant increase in the incidence of bone metastasis in thepro-arthritic and arthritic mice compared to non-arthritic controlmice. We also report that the metastatic breast cancer cellsaugment the severity of arthritis resulting in a vicious cycle thatincreases both bone destruction and metastasis. Enhancedneutrophilic and granulocytic infiltration in lungs and bone of thepro-arthritic and arthritic mice and subsequent increase incirculating levels of proinflammatory cytokines, such as macrophagecolony 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 theincreased metastasis. Treatment with anti-IL17 + celecoxib, ananti-inflammatory drug completely abrogated the development ofmetastasis and significantly reduced the primary tumorburden.
Conclusions
The data clearly has important clinical implications for patientsdiagnosed with metastatic breast cancer, especially with regards tothe prognosis and treatment options.
Abstract 1 Evaluation: Trace the use of the scientific method thatwas used in this study- include a statement of the hypothesis andan analysis of their experimental design. You do not need to knowwhat the specific molecules called âcytokinesâ are â just realizethat when they are made in a tissue they increase the level ofinflammation.
Abstract 1
Breast cancer-associated metastasis is significantly increased ina
model of autoimmune arthritis
Lopamudra Das Roy,1,2 Latha B Pathangey,1 Teresa L Tinder,1,2 JorgeL Schettini,1,2 Helen E Gruber,3 and Pinku Mukherjee1,2
Breast Cancer Res. 2009; 11(4): R56.
Introduction
Sites of chronic inflammation are often associated with theestablishment and growth of various malignancies including breastcancer. A common inflammatory condition in humans is autoimmunearthritis (AA) that causes inflammation and deformity of thejoints. Other systemic effects associated with arthritis includeincreased cellular infiltration and inflammation of the lungs.Several studies have reported statistically significant risk ratiosbetween AA and breast cancer. Despite this knowledge, available fora decade, it has never been questioned if the site of chronicinflammation linked to AA creates a milieu that attracts tumorcells to home and grow in the inflamed bones and lungs which arefrequent sites of breast cancer metastasis.
Methods
To determine if chronic inflammation induced by autoimmunearthritis contributes to increased breast cancer-associatedmetastasis, we generated mammary gland tumors in SKG mice that weregenetically prone to develop AA. Two breast cancer cell lines, onehighly metastatic (4T1) and the other non-metastatic (TUBO) wereused to generate the tumors in the mammary fat pad. Lung and bonemetastasis and the associated inflammatory milieu were evaluated inthe arthritic versus the non-arthritic mice.
Results
We report a three-fold increase in lung metastasis and asignificant increase in the incidence of bone metastasis in thepro-arthritic and arthritic mice compared to non-arthritic controlmice. We also report that the metastatic breast cancer cellsaugment the severity of arthritis resulting in a vicious cycle thatincreases both bone destruction and metastasis. Enhancedneutrophilic and granulocytic infiltration in lungs and bone of thepro-arthritic and arthritic mice and subsequent increase incirculating levels of proinflammatory cytokines, such as macrophagecolony 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 theincreased metastasis. Treatment with anti-IL17 + celecoxib, ananti-inflammatory drug completely abrogated the development ofmetastasis and significantly reduced the primary tumorburden.
Conclusions
The data clearly has important clinical implications for patientsdiagnosed with metastatic breast cancer, especially with regards tothe prognosis and treatment options.
Abstract 1 Evaluation: Trace the use of the scientific method thatwas used in this study- include a statement of the hypothesis andan analysis of their experimental design. You do not need to knowwhat the specific molecules called âcytokinesâ are â just realizethat when they are made in a tissue they increase the level ofinflammation.
Breast cancer-associated metastasis is significantly increased ina
model of autoimmune arthritis
Lopamudra Das Roy,1,2 Latha B Pathangey,1 Teresa L Tinder,1,2 JorgeL Schettini,1,2 Helen E Gruber,3 and Pinku Mukherjee1,2
Breast Cancer Res. 2009; 11(4): R56.
Introduction
Sites of chronic inflammation are often associated with theestablishment and growth of various malignancies including breastcancer. A common inflammatory condition in humans is autoimmunearthritis (AA) that causes inflammation and deformity of thejoints. Other systemic effects associated with arthritis includeincreased cellular infiltration and inflammation of the lungs.Several studies have reported statistically significant risk ratiosbetween AA and breast cancer. Despite this knowledge, available fora decade, it has never been questioned if the site of chronicinflammation linked to AA creates a milieu that attracts tumorcells to home and grow in the inflamed bones and lungs which arefrequent sites of breast cancer metastasis.
Methods
To determine if chronic inflammation induced by autoimmunearthritis contributes to increased breast cancer-associatedmetastasis, we generated mammary gland tumors in SKG mice that weregenetically prone to develop AA. Two breast cancer cell lines, onehighly metastatic (4T1) and the other non-metastatic (TUBO) wereused to generate the tumors in the mammary fat pad. Lung and bonemetastasis and the associated inflammatory milieu were evaluated inthe arthritic versus the non-arthritic mice.
Results
We report a three-fold increase in lung metastasis and asignificant increase in the incidence of bone metastasis in thepro-arthritic and arthritic mice compared to non-arthritic controlmice. We also report that the metastatic breast cancer cellsaugment the severity of arthritis resulting in a vicious cycle thatincreases both bone destruction and metastasis. Enhancedneutrophilic and granulocytic infiltration in lungs and bone of thepro-arthritic and arthritic mice and subsequent increase incirculating levels of proinflammatory cytokines, such as macrophagecolony 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 theincreased metastasis. Treatment with anti-IL17 + celecoxib, ananti-inflammatory drug completely abrogated the development ofmetastasis and significantly reduced the primary tumorburden.
Conclusions
The data clearly has important clinical implications for patientsdiagnosed with metastatic breast cancer, especially with regards tothe prognosis and treatment options.
Abstract 1 Evaluation: Trace the use of the scientific method thatwas used in this study- include a statement of the hypothesis andan analysis of their experimental design. You do not need to knowwhat the specific molecules called âcytokinesâ are â just realizethat when they are made in a tissue they increase the level ofinflammation.
Collen VonLv2
28 Sep 2019
