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CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer
Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogen...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837080/ https://www.ncbi.nlm.nih.gov/pubmed/36635273 http://dx.doi.org/10.1038/s41467-023-35793-w |
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| author | Houthuijzen, Julia M. de Bruijn, Roebi van der Burg, Eline Drenth, Anne Paulien Wientjens, Ellen Filipovic, Tamara Bullock, Esme Brambillasca, Chiara S. Pulver, Emilia M. Nieuwland, Marja de Rink, Iris van Diepen, Frank Klarenbeek, Sjoerd Kerkhoven, Ron Brunton, Valerie G. Scheele, Colinda L.G.J. Boelens, Mirjam C. Jonkers, Jos |
| author_facet | Houthuijzen, Julia M. de Bruijn, Roebi van der Burg, Eline Drenth, Anne Paulien Wientjens, Ellen Filipovic, Tamara Bullock, Esme Brambillasca, Chiara S. Pulver, Emilia M. Nieuwland, Marja de Rink, Iris van Diepen, Frank Klarenbeek, Sjoerd Kerkhoven, Ron Brunton, Valerie G. Scheele, Colinda L.G.J. Boelens, Mirjam C. Jonkers, Jos |
| author_sort | Houthuijzen, Julia M. |
| collection | PubMed |
| description | Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice, we show that CAFs in both invasive lobular breast cancer and triple-negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo and in vitro studies reveal the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. Functional co-culture experiments show that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data suggest that CD26+ and CD26- NFs transform into distinct CAF subpopulations in mouse models of breast cancer. |
| format | Online Article Text |
| id | pubmed-9837080 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-98370802023-01-14 CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer Houthuijzen, Julia M. de Bruijn, Roebi van der Burg, Eline Drenth, Anne Paulien Wientjens, Ellen Filipovic, Tamara Bullock, Esme Brambillasca, Chiara S. Pulver, Emilia M. Nieuwland, Marja de Rink, Iris van Diepen, Frank Klarenbeek, Sjoerd Kerkhoven, Ron Brunton, Valerie G. Scheele, Colinda L.G.J. Boelens, Mirjam C. Jonkers, Jos Nat Commun Article Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies. Through various transplantation studies in mice, we show that CAFs in both invasive lobular breast cancer and triple-negative breast cancer originate from mammary tissue-resident normal fibroblasts (NFs). Single-cell transcriptomics, in vivo and in vitro studies reveal the transition of CD26+ and CD26- NF populations into inflammatory CAFs (iCAFs) and myofibroblastic CAFs (myCAFs), respectively. Functional co-culture experiments show that CD26+ NFs transition into pro-tumorigenic iCAFs which recruit myeloid cells in a CXCL12-dependent manner and enhance tumor cell invasion via matrix-metalloproteinase (MMP) activity. Together, our data suggest that CD26+ and CD26- NFs transform into distinct CAF subpopulations in mouse models of breast cancer. Nature Publishing Group UK 2023-01-12 /pmc/articles/PMC9837080/ /pubmed/36635273 http://dx.doi.org/10.1038/s41467-023-35793-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Houthuijzen, Julia M. de Bruijn, Roebi van der Burg, Eline Drenth, Anne Paulien Wientjens, Ellen Filipovic, Tamara Bullock, Esme Brambillasca, Chiara S. Pulver, Emilia M. Nieuwland, Marja de Rink, Iris van Diepen, Frank Klarenbeek, Sjoerd Kerkhoven, Ron Brunton, Valerie G. Scheele, Colinda L.G.J. Boelens, Mirjam C. Jonkers, Jos CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title | CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title_full | CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title_fullStr | CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title_full_unstemmed | CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title_short | CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer |
| title_sort | cd26-negative and cd26-positive tissue-resident fibroblasts contribute to functionally distinct caf subpopulations in breast cancer |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9837080/ https://www.ncbi.nlm.nih.gov/pubmed/36635273 http://dx.doi.org/10.1038/s41467-023-35793-w |
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