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MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer
BACKGROUND: Cancer-associated fibroblasts (CAFs) are known to impact on tumour behaviour, but the mechanisms controlling this are poorly understood. METHODS: Breast normal fibroblasts (NFs) or CAFs were isolated from cancers by laser microdissection or were cultured. Fibroblasts were transfected to...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889135/ https://www.ncbi.nlm.nih.gov/pubmed/31481734 http://dx.doi.org/10.1038/s41416-019-0566-7 |
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author | Chatterjee, Annesha Jana, Samir Chatterjee, Soumya Wastall, Laura M Mandal, Gunjan Nargis, Nelofar Roy, Himansu Hughes, Thomas A Bhattacharyya, Arindam |
author_facet | Chatterjee, Annesha Jana, Samir Chatterjee, Soumya Wastall, Laura M Mandal, Gunjan Nargis, Nelofar Roy, Himansu Hughes, Thomas A Bhattacharyya, Arindam |
author_sort | Chatterjee, Annesha |
collection | PubMed |
description | BACKGROUND: Cancer-associated fibroblasts (CAFs) are known to impact on tumour behaviour, but the mechanisms controlling this are poorly understood. METHODS: Breast normal fibroblasts (NFs) or CAFs were isolated from cancers by laser microdissection or were cultured. Fibroblasts were transfected to manipulate miR-222 or Lamin B receptor (LBR). The fibroblast-conditioned medium was collected and used to treat epithelial BC lines MDA-MB-231 and MDA-MB-157. Migration, invasion, proliferation or senescence was assessed using transwell, MTT or X-gal assays, respectively. RESULTS: MiR-222 was upregulated in CAFs as compared with NFs. Ectopic miR-222 expression in NFs induced CAF-like expression profiles, while miR-222 knockdown in CAFs inhibited CAF phenotypes. LBR was identified as a direct miR-222 target, and was functionally relevant since LBR knockdown phenocopied miR-222 overexpression and LBR overexpression phenocopied miR-222 knockdown. MiR-222 overexpression, or LBR knockdown, was sufficient to induce NFs to show the CAF characteristics of enhanced migration, invasion and senescence, and furthermore, the conditioned medium from these fibroblasts induced increased BC cell migration and invasion. The reverse manipulations in CAFs inhibited these behaviours in fibroblasts, and inhibited paracrine influences on BC cells. CONCLUSION: MiR-222/LBR have key roles in controlling pro-progression influences of CAFs in BC. This pathway may present therapeutic opportunities to inhibit CAF-induced cancer progression. |
format | Online Article Text |
id | pubmed-6889135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68891352020-09-04 MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer Chatterjee, Annesha Jana, Samir Chatterjee, Soumya Wastall, Laura M Mandal, Gunjan Nargis, Nelofar Roy, Himansu Hughes, Thomas A Bhattacharyya, Arindam Br J Cancer Article BACKGROUND: Cancer-associated fibroblasts (CAFs) are known to impact on tumour behaviour, but the mechanisms controlling this are poorly understood. METHODS: Breast normal fibroblasts (NFs) or CAFs were isolated from cancers by laser microdissection or were cultured. Fibroblasts were transfected to manipulate miR-222 or Lamin B receptor (LBR). The fibroblast-conditioned medium was collected and used to treat epithelial BC lines MDA-MB-231 and MDA-MB-157. Migration, invasion, proliferation or senescence was assessed using transwell, MTT or X-gal assays, respectively. RESULTS: MiR-222 was upregulated in CAFs as compared with NFs. Ectopic miR-222 expression in NFs induced CAF-like expression profiles, while miR-222 knockdown in CAFs inhibited CAF phenotypes. LBR was identified as a direct miR-222 target, and was functionally relevant since LBR knockdown phenocopied miR-222 overexpression and LBR overexpression phenocopied miR-222 knockdown. MiR-222 overexpression, or LBR knockdown, was sufficient to induce NFs to show the CAF characteristics of enhanced migration, invasion and senescence, and furthermore, the conditioned medium from these fibroblasts induced increased BC cell migration and invasion. The reverse manipulations in CAFs inhibited these behaviours in fibroblasts, and inhibited paracrine influences on BC cells. CONCLUSION: MiR-222/LBR have key roles in controlling pro-progression influences of CAFs in BC. This pathway may present therapeutic opportunities to inhibit CAF-induced cancer progression. Nature Publishing Group UK 2019-09-04 2019-10-15 /pmc/articles/PMC6889135/ /pubmed/31481734 http://dx.doi.org/10.1038/s41416-019-0566-7 Text en © The Author(s), under exclusive licence to Cancer Research UK 2019 https://creativecommons.org/licenses/by/4.0/Note: This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0). |
spellingShingle | Article Chatterjee, Annesha Jana, Samir Chatterjee, Soumya Wastall, Laura M Mandal, Gunjan Nargis, Nelofar Roy, Himansu Hughes, Thomas A Bhattacharyya, Arindam MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title | MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title_full | MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title_fullStr | MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title_full_unstemmed | MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title_short | MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
title_sort | microrna-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889135/ https://www.ncbi.nlm.nih.gov/pubmed/31481734 http://dx.doi.org/10.1038/s41416-019-0566-7 |
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