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癌症相关成纤维细胞中钙内流途径的改变

Altered Calcium Influx Pathways in Cancer-Associated Fibroblasts.

作者信息

Sadras Francisco, Stewart Teneale A, Robitaille Mélanie, Peters Amelia A, Croft Priyakshi Kalita-de, Soon Patsy S, Saunus Jodi M, Lakhani Sunil R, Roberts-Thomson Sarah J, Monteith Gregory R

机构信息

School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia.

Mater Research, Translational Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia.

出版信息

Biomedicines. 2021 Jun 16;9(6):680. doi: 10.3390/biomedicines9060680.

DOI:10.3390/biomedicines9060680
PMID:34208665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8234491/
Abstract

Cancer-associated fibroblasts (CAFs) represent an important component of the tumour microenvironment and are implicated in disease progression. Two outstanding questions in cancer biology are how CAFs arise and how they might be targeted therapeutically. The calcium signal also has an important role in tumorigenesis. To date, the role of calcium signalling pathways in the induction of the CAF phenotype remains unexplored. A CAF model was generated through exogenous transforming growth factor beta 1 (TGFβ1) stimulation of the normal human mammary fibroblast cell line, HMF3S (HMF3S-CAF), and changes in calcium signalling were investigated. Functional changes in HMF3S-CAF calcium signalling pathways were assessed using a fluorescent indicator, gene expression, gene-silencing and pharmacological approaches. HMF3S-CAF cells demonstrated functionally altered calcium influx pathways with reduced store-operated calcium entry. In support of a calcium signalling switch, two voltage-gated calcium channel (VGCC) family members, Ca1.2 and Ca3.2, were upregulated in HMF3S-CAFs and a subset of patient-derived breast CAFs. Both siRNA-mediated silencing and pharmacological inhibition of Ca1.2 or Ca3.2 significantly impaired CAF activation in HMF3S cells. Our findings show that VGCCs contribute to TGFβ1-mediated induction of HMF3S-CAF cells and both transcriptional interference and pharmacological antagonism of Ca1.2 and Ca3.2 inhibit CAF induction. This suggests a potential therapeutic role for targeting calcium signalling in breast CAFs.

摘要

癌症相关成纤维细胞（CAFs）是肿瘤微环境的重要组成部分，与疾病进展有关。癌症生物学中有两个突出问题，即CAFs如何产生以及如何对其进行靶向治疗。钙信号在肿瘤发生中也起着重要作用。迄今为止，钙信号通路在CAF表型诱导中的作用仍未得到探索。通过外源性转化生长因子β1（TGFβ1）刺激正常人乳腺成纤维细胞系HMF3S建立了CAF模型（HMF3S-CAF），并研究了钙信号的变化。使用荧光指示剂、基因表达、基因沉默和药理学方法评估了HMF3S-CAF钙信号通路的功能变化。HMF3S-CAF细胞表现出功能改变的钙内流途径，储存-操作性钙内流减少。作为钙信号转换的证据，两个电压门控钙通道（VGCC）家族成员Ca1.2和Ca3.2在HMF3S-CAFs以及一部分患者来源的乳腺CAFs中上调。siRNA介导的Ca1.2或Ca3.2沉默以及药理学抑制均显著损害了HMF3S细胞中CAF的激活。我们的研究结果表明，VGCCs有助于TGFβ1介导的HMF3S-CAF细胞诱导，对Ca1.2和Ca3.2的转录干扰和药理学拮抗均抑制CAF诱导。这表明靶向乳腺CAFs中的钙信号具有潜在的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/849d9b84fa4c/biomedicines-09-00680-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/ec7c1fa0a345/biomedicines-09-00680-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/07896c796f36/biomedicines-09-00680-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/f9f855f3fb9f/biomedicines-09-00680-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/d454eacca86a/biomedicines-09-00680-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/849d9b84fa4c/biomedicines-09-00680-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/ec7c1fa0a345/biomedicines-09-00680-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/07896c796f36/biomedicines-09-00680-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/f9f855f3fb9f/biomedicines-09-00680-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/d454eacca86a/biomedicines-09-00680-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a7/8234491/849d9b84fa4c/biomedicines-09-00680-g005.jpg

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3
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