Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.
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DOI：
10.1038/s41419-023-06240-x
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发表时间：
2023-11-08
影响因子：
9
通讯作者：
Pardo, Olivier E.
中科院分区：
文献类型：
--
作者：
Chrisochoidou, Yakinthi;Roy, Rajat;Farahmand, Pooyeh;Gonzalez, Guadalupe;Doig, Jennifer;Krasny, Lukas;Rimmer, Ella F.;Willis, Anne E.;MacFarlane, Marion;Huang, Paul H.;Carragher, Neil O.;Munro, Alison F.;Murphy, Daniel J.;Veselkov, Kirill;Seckl, Michael J.;Moffatt, Miriam F.;Cookson, William O. C.;Pardo, Olivier E.
间皮瘤是一种侵袭性的间皮层癌，伴有广泛的纤维化反应。后者在很大程度上是由癌症相关成纤维细胞介导的，这些成纤维细胞介导了肿瘤的进展和不良的预后。然而，对于这种疾病中癌细胞和成纤维细胞之间的串扰，人们大多缺乏了解。在这里，使用患者来源的间皮瘤细胞系和肺成纤维细胞的共培养，我们证明成纤维细胞的激活是一个自我繁殖的过程，产生纤维化的细胞外基质(ECM)，并在间皮瘤细胞中触发耐药性。根据间皮瘤细胞/成纤维细胞信号串扰的特征，我们发现FDA批准的几种靶向疗法在ECM嵌入的共培养球体模型中比标准护理顺铂/培美曲塞有效得多。特别是，SRC家族激酶抑制剂沙拉卡替尼在间皮瘤基因工程小鼠模型中延长了总生存期，远远超出了标准护理。总之，我们为合理设计针对间皮瘤/成纤维细胞通讯的新的治疗策略治疗间皮瘤患者奠定了基础。
Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients.
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影响因子：
5.6
作者：
通讯作者：
--
癌症相关成纤维细胞的生物标志物
影响因子：
11.1
作者：
Han C;Liu T;Yin R
通讯作者：
Yin R
DOI：
10.1084/jem.20191257
发表时间：
2020-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Badhai J;Pandey GK;Song JY;Krijgsman O;Bhaskaran R;Chandrasekaran G;Kwon MC;Bombardelli L;Monkhorst K;Grasso C;Zevenhoven J;van der Vliet J;Cozijnsen M;Krimpenfort P;Peeper D;van Lohuizen M;Berns A
通讯作者：
Berns A
影响因子：
--
作者：
Heusschen R;Muller J;Binsfeld M;Marty C;Plougonven E;Dubois S;Mahli N;Moermans K;Carmeliet G;Léonard A;Baron F;Beguin Y;Menu E;Cohen-Solal M;Caers J
通讯作者：
Caers J
影响因子：
5.8
作者：
Hung CF;Rohani MG;Lee SS;Chen P;Schnapp LM
通讯作者：
Schnapp LM