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Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment
Recent reports show that colorectal tumors contain microbiota that are distinct from those that reside in a ‘normal’ colon environment, and that these microbiota can contribute to cancer progression. Fusobacterium nucleatum is the most commonly observed species in the colorectal tumor microenvironme...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093526/ https://www.ncbi.nlm.nih.gov/pubmed/32210258 http://dx.doi.org/10.1038/s41598-020-62139-z |
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author | Kasper, Stephen H. Morell-Perez, Carolina Wyche, Thomas P. Sana, Theodore R. Lieberman, Linda A. Hett, Erik C. |
author_facet | Kasper, Stephen H. Morell-Perez, Carolina Wyche, Thomas P. Sana, Theodore R. Lieberman, Linda A. Hett, Erik C. |
author_sort | Kasper, Stephen H. |
collection | PubMed |
description | Recent reports show that colorectal tumors contain microbiota that are distinct from those that reside in a ‘normal’ colon environment, and that these microbiota can contribute to cancer progression. Fusobacterium nucleatum is the most commonly observed species in the colorectal tumor microenvironment and reportedly influences disease progression through numerous mechanisms. However, a detailed understanding of the role of this organism in cancer progression is limited, in part due to challenges in maintaining F. nucleatum viability under standard aerobic cell culture conditions. Herein we describe the development of a 3-dimensional (3D) tumor spheroid model that can harbor and promote the growth of anaerobic bacteria. Bacteria-tumor cell interactions and metabolic crosstalk were extensively studied by measuring the kinetics of bacterial growth, cell morphology and lysis, cancer-related gene expression, and metabolomics. We observed that viable F. nucleatum assembles biofilm-like structures in the tumor spheroid microenvironment, whereas heat-killed F. nucleatum is internalized and sequestered in the cancer cells. Lastly, we use the model to co-culture 28 Fusobacterium clinical isolates and demonstrate that the model successfully supports co-culture with diverse fusobacterial species. This bacteria-spheroid co-culture model enables mechanistic investigation of the role of anaerobic bacteria in the tumor microenvironment. |
format | Online Article Text |
id | pubmed-7093526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70935262020-03-27 Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment Kasper, Stephen H. Morell-Perez, Carolina Wyche, Thomas P. Sana, Theodore R. Lieberman, Linda A. Hett, Erik C. Sci Rep Article Recent reports show that colorectal tumors contain microbiota that are distinct from those that reside in a ‘normal’ colon environment, and that these microbiota can contribute to cancer progression. Fusobacterium nucleatum is the most commonly observed species in the colorectal tumor microenvironment and reportedly influences disease progression through numerous mechanisms. However, a detailed understanding of the role of this organism in cancer progression is limited, in part due to challenges in maintaining F. nucleatum viability under standard aerobic cell culture conditions. Herein we describe the development of a 3-dimensional (3D) tumor spheroid model that can harbor and promote the growth of anaerobic bacteria. Bacteria-tumor cell interactions and metabolic crosstalk were extensively studied by measuring the kinetics of bacterial growth, cell morphology and lysis, cancer-related gene expression, and metabolomics. We observed that viable F. nucleatum assembles biofilm-like structures in the tumor spheroid microenvironment, whereas heat-killed F. nucleatum is internalized and sequestered in the cancer cells. Lastly, we use the model to co-culture 28 Fusobacterium clinical isolates and demonstrate that the model successfully supports co-culture with diverse fusobacterial species. This bacteria-spheroid co-culture model enables mechanistic investigation of the role of anaerobic bacteria in the tumor microenvironment. Nature Publishing Group UK 2020-03-24 /pmc/articles/PMC7093526/ /pubmed/32210258 http://dx.doi.org/10.1038/s41598-020-62139-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kasper, Stephen H. Morell-Perez, Carolina Wyche, Thomas P. Sana, Theodore R. Lieberman, Linda A. Hett, Erik C. Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title_full | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title_fullStr | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title_full_unstemmed | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title_short | Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
title_sort | colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093526/ https://www.ncbi.nlm.nih.gov/pubmed/32210258 http://dx.doi.org/10.1038/s41598-020-62139-z |
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