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Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis

Metastasis is the primary cause of a large number of cancer-associated deaths. By portraying the precise environment of the metastasis process in vitro, the microfluidic system provides useful insights on the mechanisms underlying cancer cell migration, invasion, colonization, and the procurement of...

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Autores principales: Cho, Hyeon-Yeol, Choi, Jin-Ha, Kim, Kyeong-Jun, Shin, Minkyu, Choi, Jeong-Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917128/
https://www.ncbi.nlm.nih.gov/pubmed/33659239
http://dx.doi.org/10.3389/fbioe.2020.611802
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author Cho, Hyeon-Yeol
Choi, Jin-Ha
Kim, Kyeong-Jun
Shin, Minkyu
Choi, Jeong-Woo
author_facet Cho, Hyeon-Yeol
Choi, Jin-Ha
Kim, Kyeong-Jun
Shin, Minkyu
Choi, Jeong-Woo
author_sort Cho, Hyeon-Yeol
collection PubMed
description Metastasis is the primary cause of a large number of cancer-associated deaths. By portraying the precise environment of the metastasis process in vitro, the microfluidic system provides useful insights on the mechanisms underlying cancer cell migration, invasion, colonization, and the procurement of supplemental nutrients. However, current in vitro metastasis models are biased in studying blood vessel-based metastasis pathways and thus the understanding of lymphatic metastasis is limited which is also closely related to the inflammatory system. To understand the effects of inflammatory cytokines in lymphatic metastasis, we developed a three-channel microfluidic system by mimicking the lymph vessel-tissue-blood vessel (LTB) structure. Based on the LTB chip, we successfully confirmed the inflammatory cytokine, interleukin 6 (IL-6), -mediated intercellular communication in the tumor microenvironment during lymphatic metastasis. The IL-6 exposure to different subtypes of breast cancer cells was induced epithelial-mesenchymal transition (EMT) and improved tissue invasion property (8-fold). And the growth of human vein endothelial cells toward the lymph vessel channel was observed by VEGF secretion from human lymphatic endothelial cells with IL-6 treatment. The proposed LTB chip can be applied to analyze the intercellular communication during the lymphatic metastasis process and be a unique tool to understand the intercellular communication in the cancer microenvironment under various extracellular stimuli such as inflammatory cytokines, stromal reactions, hypoxia, and nutrient deficiency.
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spelling pubmed-79171282021-03-02 Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis Cho, Hyeon-Yeol Choi, Jin-Ha Kim, Kyeong-Jun Shin, Minkyu Choi, Jeong-Woo Front Bioeng Biotechnol Bioengineering and Biotechnology Metastasis is the primary cause of a large number of cancer-associated deaths. By portraying the precise environment of the metastasis process in vitro, the microfluidic system provides useful insights on the mechanisms underlying cancer cell migration, invasion, colonization, and the procurement of supplemental nutrients. However, current in vitro metastasis models are biased in studying blood vessel-based metastasis pathways and thus the understanding of lymphatic metastasis is limited which is also closely related to the inflammatory system. To understand the effects of inflammatory cytokines in lymphatic metastasis, we developed a three-channel microfluidic system by mimicking the lymph vessel-tissue-blood vessel (LTB) structure. Based on the LTB chip, we successfully confirmed the inflammatory cytokine, interleukin 6 (IL-6), -mediated intercellular communication in the tumor microenvironment during lymphatic metastasis. The IL-6 exposure to different subtypes of breast cancer cells was induced epithelial-mesenchymal transition (EMT) and improved tissue invasion property (8-fold). And the growth of human vein endothelial cells toward the lymph vessel channel was observed by VEGF secretion from human lymphatic endothelial cells with IL-6 treatment. The proposed LTB chip can be applied to analyze the intercellular communication during the lymphatic metastasis process and be a unique tool to understand the intercellular communication in the cancer microenvironment under various extracellular stimuli such as inflammatory cytokines, stromal reactions, hypoxia, and nutrient deficiency. Frontiers Media S.A. 2021-02-15 /pmc/articles/PMC7917128/ /pubmed/33659239 http://dx.doi.org/10.3389/fbioe.2020.611802 Text en Copyright © 2021 Cho, Choi, Kim, Shin and Choi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Cho, Hyeon-Yeol
Choi, Jin-Ha
Kim, Kyeong-Jun
Shin, Minkyu
Choi, Jeong-Woo
Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title_full Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title_fullStr Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title_full_unstemmed Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title_short Microfluidic System to Analyze the Effects of Interleukin 6 on Lymphatic Breast Cancer Metastasis
title_sort microfluidic system to analyze the effects of interleukin 6 on lymphatic breast cancer metastasis
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917128/
https://www.ncbi.nlm.nih.gov/pubmed/33659239
http://dx.doi.org/10.3389/fbioe.2020.611802
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