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dc.contributor.authorGómez-Cuadrado, L
dc.contributor.authorBullock, E
dc.contributor.authorMabruk, Z
dc.contributor.authorZhao, H
dc.contributor.authorSouleimanova, M
dc.contributor.authorNoer, PR
dc.contributor.authorTurnbull, AK
dc.contributor.authorOxvig, C
dc.contributor.authorBertos, N
dc.contributor.authorByron, A
dc.contributor.authorDixon, JM
dc.contributor.authorPark, M
dc.contributor.authorHaider, S
dc.contributor.authorNatrajan, R
dc.contributor.authorSims, AH
dc.contributor.authorBrunton, VG
dc.date.accessioned2022-05-04T12:48:11Z
dc.date.available2022-05-04T12:48:11Z
dc.date.issued2022-02-11
dc.identifier.citationCancers, 2022, 14 (4)en
dc.identifier.issn2072-6694
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5109
dc.identifier.eissn2072-6694en_US
dc.identifier.eissn2072-6694
dc.identifier.doi10.3390/cancers14040904en_US
dc.identifier.doi10.3390/cancers14040904
dc.description.abstractInvasive 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 <i>PAPPA</i> and <i>TIMP2</i> being associated with better survival in ILC but not IDC. <i>PAPPA,</i> a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of <i>PAPPA</i>- and <i>IGF1</i>-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.en_US
dc.formatElectronicen_US
dc.languageengen_US
dc.language.isoengen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleCharacterisation of the Stromal Microenvironment in Lobular Breast Cancer.en
dc.typeJournal Article
dcterms.dateAccepted2022-02-06
rioxxterms.versionVoRen
rioxxterms.versionofrecord10.3390/cancers14040904en
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en
rioxxterms.licenseref.startdate2022-02-11
dc.relation.isPartOfCancersen_US
pubs.issue4en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/ImmNet
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
pubs.publication-statusPublisheden_US
pubs.volume14en_US
pubs.embargo.termsNot knownen_US
icr.researchteamFunctional Genomics
dc.contributor.icrauthorNatrajan, Rachaelen_US
dc.contributor.icrauthorHaider, Syeden_US


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