RT info:eu-repo/semantics/article
T1 Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
A1 Gómez Cuadrado, Laura
A1 Bullock, Esme
A1 Mabruk, Zeanap
A1 Zhao, Hong
A1 Souleimanova, Margarita
A1 Noer, Pernille Rimmer
A1 Turnbull, Arran K.
A1 Oxvig, Claus
A1 Bertos, Nicholas
A1 Byron, Adam
A1 Dixon, J. Michael
A1 Park, Morag
A1 Haider, Syed
A1 Natrajan, Rachael
A1 Sims, Andrew H.
A1 Brunton, Valerie G.
K1 Lobular breast cancer
K1 Tumor microenvironment
K1 Cancer-associated fibroblasts
K1 Oncología
K1 Oncology
K1 Salud
K1 Health
K1 Medicina
K1 Medicine
AB 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.
PB MDPI
YR 2022
FD 2022-02
LK http://hdl.handle.net/10259/9801
UL http://hdl.handle.net/10259/9801
LA eng
NO 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.).
DS Repositorio Institucional de la Universidad de Burgos
RD 21-ene-2025