TY - JOUR
KW - Bone metastasis
KW - Breast cancer
KW - IL, interleukin
KW - IL-6, interleukin 6
KW - MCP-1, monocyte chemoattractant protein 1
KW - MIP-1α, macrophage inflammatory protein 1α
KW - Metastasis-on-a-chip
KW - NE, norepinephrine
KW - PDMS, poly-dimethylsiloxane
KW - Paracrine
KW - SNS, Sympathetic Nervous System
KW - Sympathetic nervous system
KW - TH, tyrosine hydroxylase
AU - Francisco Conceição
AU - Daniela M. Sousa
AU - Joshua Loessberg-Zahl
AU - Anke R. Vollertsen
AU - Estrela Neto
AU - Kent Søe
AU - Joana Paredes
AU - Anne Leferink
AU - Meriem Lamghari
AB - 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.
BT - Materials Today. Bio
DA - 2022-01
DO - 10.1016/j.mtbio.2022.100219
LA - eng
N2 - 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.
PY - 2022
EP - 100219
T2 - Materials Today. Bio
TI - A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis
VL - 13
SN - 2590-0064
ER -