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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2014
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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. |
format | Online Article Text |
id | pubmed-4240917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
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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