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...

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Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Burgos (UBU)
Repositorio:Repositorio Institucional de la Universidad de Burgos (RIUBU)
OAI Identifier:oai:riubu.ubu.es:10259/9801
Acceso en línea:http://hdl.handle.net/10259/9801
Access Level:acceso abierto
Palabra clave:Lobular breast cancer
Tumor microenvironment
Cancer-associated fibroblasts
Oncología
Oncology
Salud
Health
Medicina
Medicine
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spelling Characterisation of the Stromal Microenvironment in Lobular Breast CancerGómez Cuadrado, LauraBullock, EsmeMabruk, ZeanapZhao, HongSouleimanova, MargaritaNoer, Pernille RimmerTurnbull, Arran K.Oxvig, ClausBertos, NicholasByron, AdamDixon, J. MichaelPark, MoragHaider, SyedNatrajan, RachaelSims, Andrew H.Brunton, Valerie G.Lobular breast cancerTumor microenvironmentCancer-associated fibroblastsOncologíaOncologySaludHealthMedicinaMedicinenvasive 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.).MDPI202420242022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10259/9801reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)instname:Universidad de Burgos (UBU)InglésCancers. 2022, V. 14, n. 4, p. 904https://doi.org/10.3390/cancers14040904Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riubu.ubu.es:10259/98012026-05-28T07:56:11Z
dc.title.none.fl_str_mv Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
title Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
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
title_short 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_sort Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
dc.creator.none.fl_str_mv 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 Gómez Cuadrado, Laura
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
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
dc.subject.none.fl_str_mv Lobular breast cancer
Tumor microenvironment
Cancer-associated fibroblasts
Oncología
Oncology
Salud
Health
Medicina
Medicine
topic Lobular breast cancer
Tumor microenvironment
Cancer-associated fibroblasts
Oncología
Oncology
Salud
Health
Medicina
Medicine
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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10259/9801
url http://hdl.handle.net/10259/9801
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cancers. 2022, V. 14, n. 4, p. 904
https://doi.org/10.3390/cancers14040904
dc.rights.none.fl_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Institucional de la Universidad de Burgos (RIUBU)
instname:Universidad de Burgos (UBU)
instname_str Universidad de Burgos (UBU)
reponame_str Repositorio Institucional de la Universidad de Burgos (RIUBU)
collection Repositorio Institucional de la Universidad de Burgos (RIUBU)
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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