Cancer-associated fibroblasts promote cisplatin resistance in bladder cancer cells by increasing IGF-1/ERβ/Bcl-2 signalling
| العنوان: | Cancer-associated fibroblasts promote cisplatin resistance in bladder cancer cells by increasing IGF-1/ERβ/Bcl-2 signalling |
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| المؤلفون: | Yi Cai, Lin Qi, Miao Mo, Xingbo Long, Zhi Chen, Yuan Li, Wei Xiong, Xiting Zeng, Huichuan Jiang, Bisong Zhu |
| المصدر: | Cell Death and Disease, Vol 10, Iss 5, Pp 1-16 (2019) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cancer microenvironment, 0301 basic medicine, Cancer Research, Urinary Bladder, Immunology, Clone (cell biology), Mice, Nude, Apoptosis, Kaplan-Meier Estimate, Article, Cell Line, Small hairpin RNA, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cancer-Associated Fibroblasts, Stroma, medicine, Animals, Estrogen Receptor beta, Humans, Chemotherapy, Insulin-Like Growth Factor I, RNA, Small Interfering, lcsh:QH573-671, skin and connective tissue diseases, Cisplatin, Bladder cancer, Chemistry, lcsh:Cytology, JNK Mitogen-Activated Protein Kinases, Cell Biology, medicine.disease, 030104 developmental biology, Proto-Oncogene Proteins c-bcl-2, Urinary Bladder Neoplasms, Drug Resistance, Neoplasm, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Female, RNA Interference, Signal Transduction, medicine.drug |
| الوصف: | While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERβ in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERβ expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERβ signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERβ/Bcl-2 signalling by either an shRNA targeting ERβ or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERβ/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::074edd1c05e667785bb747efe7d611cb http://link.springer.com/article/10.1038/s41419-019-1581-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....074edd1c05e667785bb747efe7d611cb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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