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A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis

Organ-on-a-chip models have emerged as a powerful tool to model cancer metastasis and to decipher specific crosstalk between cancer cells and relevant regulators of this particular niche. Recently, the sympathetic nervous system (SNS) was proposed as an important modulator of breast cancer bone meta...

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Autores principales: Conceição, Francisco, Sousa, Daniela M., Loessberg-Zahl, Joshua, Vollertsen, Anke R., Neto, Estrela, Søe, Kent, Paredes, Joana, Leferink, Anne, Lamghari, Meriem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857466/
https://www.ncbi.nlm.nih.gov/pubmed/35243294
http://dx.doi.org/10.1016/j.mtbio.2022.100219
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author Conceição, Francisco
Sousa, Daniela M.
Loessberg-Zahl, Joshua
Vollertsen, Anke R.
Neto, Estrela
Søe, Kent
Paredes, Joana
Leferink, Anne
Lamghari, Meriem
author_facet Conceição, Francisco
Sousa, Daniela M.
Loessberg-Zahl, Joshua
Vollertsen, Anke R.
Neto, Estrela
Søe, Kent
Paredes, Joana
Leferink, Anne
Lamghari, Meriem
author_sort Conceição, Francisco
collection PubMed
description Organ-on-a-chip models have emerged as a powerful tool to model cancer metastasis and to decipher specific crosstalk between cancer cells and relevant regulators of this particular niche. Recently, the sympathetic nervous system (SNS) was proposed as an important modulator of breast cancer bone metastasis. However, epidemiological studies concerning the benefits of the SNS targeting drugs on breast cancer survival and recurrence remain controversial. Thus, the role of SNS signaling over bone metastatic cancer cellular processes still requires further clarification. Herein, we present a novel humanized organ-on-a-chip model recapitulating neuro-breast cancer crosstalk in a bone metastatic context. We developed and validated an innovative three-dimensional printing based multi-compartment microfluidic platform, allowing both selective and dynamic multicellular paracrine signaling between sympathetic neurons, bone tropic breast cancer cells and osteoclasts. The selective multicellular crosstalk in combination with biochemical, microscopic and proteomic profiling show that synergistic paracrine signaling from sympathetic neurons and osteoclasts increase breast cancer aggressiveness demonstrated by augmented levels of pro-inflammatory cytokines (e.g. interleukin-6 and macrophage inflammatory protein 1α). Overall, this work introduced a novel and versatile platform that could potentially be used to unravel new mechanisms involved in intracellular communication at the bone metastatic niche.
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spelling pubmed-88574662022-03-02 A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis Conceição, Francisco Sousa, Daniela M. Loessberg-Zahl, Joshua Vollertsen, Anke R. Neto, Estrela Søe, Kent Paredes, Joana Leferink, Anne Lamghari, Meriem Mater Today Bio Full Length Article Organ-on-a-chip models have emerged as a powerful tool to model cancer metastasis and to decipher specific crosstalk between cancer cells and relevant regulators of this particular niche. Recently, the sympathetic nervous system (SNS) was proposed as an important modulator of breast cancer bone metastasis. However, epidemiological studies concerning the benefits of the SNS targeting drugs on breast cancer survival and recurrence remain controversial. Thus, the role of SNS signaling over bone metastatic cancer cellular processes still requires further clarification. Herein, we present a novel humanized organ-on-a-chip model recapitulating neuro-breast cancer crosstalk in a bone metastatic context. We developed and validated an innovative three-dimensional printing based multi-compartment microfluidic platform, allowing both selective and dynamic multicellular paracrine signaling between sympathetic neurons, bone tropic breast cancer cells and osteoclasts. The selective multicellular crosstalk in combination with biochemical, microscopic and proteomic profiling show that synergistic paracrine signaling from sympathetic neurons and osteoclasts increase breast cancer aggressiveness demonstrated by augmented levels of pro-inflammatory cytokines (e.g. interleukin-6 and macrophage inflammatory protein 1α). Overall, this work introduced a novel and versatile platform that could potentially be used to unravel new mechanisms involved in intracellular communication at the bone metastatic niche. Elsevier 2022-02-14 /pmc/articles/PMC8857466/ /pubmed/35243294 http://dx.doi.org/10.1016/j.mtbio.2022.100219 Text en © 2022 The Authors. Published by Elsevier Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Full Length Article
Conceição, Francisco
Sousa, Daniela M.
Loessberg-Zahl, Joshua
Vollertsen, Anke R.
Neto, Estrela
Søe, Kent
Paredes, Joana
Leferink, Anne
Lamghari, Meriem
A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title_full A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title_fullStr A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title_full_unstemmed A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title_short A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
title_sort metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857466/
https://www.ncbi.nlm.nih.gov/pubmed/35243294
http://dx.doi.org/10.1016/j.mtbio.2022.100219
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