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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...

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Detalles Bibliográficos
Autores principales: Chatterjee, Annesha, Jana, Samir, Chatterjee, Soumya, Wastall, Laura M, Mandal, Gunjan, Nargis, Nelofar, Roy, Himansu, Hughes, Thomas A, Bhattacharyya, Arindam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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