Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
nvasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of I...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2022 |
| Country: | España |
| Institution: | Universidad de Burgos (UBU) |
| Repository: | Repositorio Institucional de la Universidad de Burgos (RIUBU) |
| OAI Identifier: | oai:riubu.ubu.es:10259/9801 |
| Online Access: | http://hdl.handle.net/10259/9801 |
| Access Level: | Open access |
| Keyword: | Lobular breast cancer Tumor microenvironment Cancer-associated fibroblasts Oncología Oncology Salud Health Medicina Medicine |
| _version_ | 1878729154636021760 |
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| author | Gómez Cuadrado, Laura |
| author2 | Bullock, Esme Mabruk, Zeanap Zhao, Hong Souleimanova, Margarita Noer, Pernille Rimmer Turnbull, Arran K. Oxvig, Claus Bertos, Nicholas Byron, Adam Dixon, J. Michael Park, Morag Haider, Syed Natrajan, Rachael Sims, Andrew H. Brunton, Valerie G. |
| author2_role | author author author author author author author author author author author author author author author |
| author_browse | Bertos, Nicholas Brunton, Valerie G. Bullock, Esme Byron, Adam Dixon, J. Michael Gómez Cuadrado, Laura Haider, Syed Mabruk, Zeanap Natrajan, Rachael Noer, Pernille Rimmer Oxvig, Claus Park, Morag Sims, Andrew H. Souleimanova, Margarita Turnbull, Arran K. Zhao, Hong |
| author_facet | Gómez Cuadrado, Laura Bullock, Esme Mabruk, Zeanap Zhao, Hong Souleimanova, Margarita Noer, Pernille Rimmer Turnbull, Arran K. Oxvig, Claus Bertos, Nicholas Byron, Adam Dixon, J. Michael Park, Morag Haider, Syed Natrajan, Rachael Sims, Andrew H. Brunton, Valerie G. |
| author_role | author |
| collection | Repositorio Institucional de la Universidad de Burgos (RIUBU) |
| description | nvasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_0270f23dfd8d10c41d70eacfc0ea875d |
| institution | Universidad de Burgos (UBU) |
| instname_str | Universidad de Burgos (UBU) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:riubu.ubu.es:10259/9801 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Repositorio Institucional de la Universidad de Burgos (RIUBU) |
| spelling | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer Gómez Cuadrado, Laura Bullock, Esme Mabruk, Zeanap Zhao, Hong Souleimanova, Margarita Noer, Pernille Rimmer Turnbull, Arran K. Oxvig, Claus Bertos, Nicholas Byron, Adam Dixon, J. Michael Park, Morag Haider, Syed Natrajan, Rachael Sims, Andrew H. Brunton, Valerie G. Lobular breast cancer Tumor microenvironment Cancer-associated fibroblasts Oncología Oncology Salud Health Medicina Medicine nvasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways. This work was funded by Cancer Research UK (C157/A23219 to LGC; C157/A29279 to E.B.) and the Cancer Research UK Edinburgh Centre Award (C157/A18075), an Endeavour Scholarship (734/2018/878 to Z.M.) and Programme Grants from Breast Cancer Now as part of Programme Funding to the Breast Cancer Now Toby Robins Research Centre (S.H. and R.N.). The breast tissue and data bank at McGill University is supported by funding from the Database and Tissue Bank Axis of the Réseau de Recherche en Cancer of the Fonds de Recherche du Québec-Santé and the Quebec Breast Cancer Foundation (to M.P.). MDPI http://hdl.handle.net/10259/9801 |
| spellingShingle | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer Gómez Cuadrado, Laura Lobular breast cancer Tumor microenvironment Cancer-associated fibroblasts Oncología Oncology Salud Health Medicina Medicine |
| status_str | publishedVersion |
| title | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| title_full | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| title_fullStr | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| title_full_unstemmed | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| title_short | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| title_sort | Characterisation of the Stromal Microenvironment in Lobular Breast Cancer |
| topic | Lobular breast cancer Tumor microenvironment Cancer-associated fibroblasts Oncología Oncology Salud Health Medicina Medicine |
| topic_facet | Lobular breast cancer Tumor microenvironment Cancer-associated fibroblasts Oncología Oncology Salud Health Medicina Medicine |
| url | http://hdl.handle.net/10259/9801 |