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Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()

INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors resu...

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Autores principales: Mathenge, Edward Gitau, Dean, Cheryl Ann, Clements, Derek, Vaghar-Kashani, Ahmad, Photopoulos, Steffany, Coyle, Krysta Mila, Giacomantonio, Michael, Malueth, Benjamin, Nunokawa, Anna, Jordan, Julie, Lewis, John D., Gujar, Shashi Ashok, Marcato, Paola, Lee, Patrick W.K., Giacomantonio, Carman Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240917/
https://www.ncbi.nlm.nih.gov/pubmed/25425969
http://dx.doi.org/10.1016/j.neo.2014.09.004
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author Mathenge, Edward Gitau
Dean, Cheryl Ann
Clements, Derek
Vaghar-Kashani, Ahmad
Photopoulos, Steffany
Coyle, Krysta Mila
Giacomantonio, Michael
Malueth, Benjamin
Nunokawa, Anna
Jordan, Julie
Lewis, John D.
Gujar, Shashi Ashok
Marcato, Paola
Lee, Patrick W.K.
Giacomantonio, Carman Anthony
author_facet Mathenge, Edward Gitau
Dean, Cheryl Ann
Clements, Derek
Vaghar-Kashani, Ahmad
Photopoulos, Steffany
Coyle, Krysta Mila
Giacomantonio, Michael
Malueth, Benjamin
Nunokawa, Anna
Jordan, Julie
Lewis, John D.
Gujar, Shashi Ashok
Marcato, Paola
Lee, Patrick W.K.
Giacomantonio, Carman Anthony
author_sort Mathenge, Edward Gitau
collection PubMed
description INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.
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spelling pubmed-42409172014-11-25 Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()() Mathenge, Edward Gitau Dean, Cheryl Ann Clements, Derek Vaghar-Kashani, Ahmad Photopoulos, Steffany Coyle, Krysta Mila Giacomantonio, Michael Malueth, Benjamin Nunokawa, Anna Jordan, Julie Lewis, John D. Gujar, Shashi Ashok Marcato, Paola Lee, Patrick W.K. Giacomantonio, Carman Anthony Neoplasia Article INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases. Neoplasia Press 2014-11-20 /pmc/articles/PMC4240917/ /pubmed/25425969 http://dx.doi.org/10.1016/j.neo.2014.09.004 Text en © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Mathenge, Edward Gitau
Dean, Cheryl Ann
Clements, Derek
Vaghar-Kashani, Ahmad
Photopoulos, Steffany
Coyle, Krysta Mila
Giacomantonio, Michael
Malueth, Benjamin
Nunokawa, Anna
Jordan, Julie
Lewis, John D.
Gujar, Shashi Ashok
Marcato, Paola
Lee, Patrick W.K.
Giacomantonio, Carman Anthony
Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title_full Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title_fullStr Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title_full_unstemmed Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title_short Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model()()
title_sort core needle biopsy of breast cancer tumors increases distant metastases in a mouse model()()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240917/
https://www.ncbi.nlm.nih.gov/pubmed/25425969
http://dx.doi.org/10.1016/j.neo.2014.09.004
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