Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7FB2372AC0AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1.
Périodique
EMBO molecular medicine
Auteur⸱e⸱s
Sflomos G., Battista L., Aouad P., De Martino F., Scabia V., Stravodimou A., Ayyanan A., Ifticene-Treboux A., Bucher P., Fiche M., Ambrosini G., Brisken C.
Collaborateur⸱rice⸱s
RLS
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Statut éditorial
Publié
Date de publication
05/03/2021
Peer-reviewed
Oui
Volume
13
Numéro
3
Pages
e13180
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Invasive lobular carcinoma (ILC) is the most frequent special histological subtype of breast cancer, typically characterized by loss of E-cadherin. It has clinical features distinct from other estrogen receptor-positive (ER <sup>+</sup> ) breast cancers but the molecular mechanisms underlying its characteristic biology are poorly understood because we lack experimental models to study them. Here, we recapitulate the human disease, including its metastatic pattern, by grafting ILC-derived breast cancer cell lines, SUM-44 PE and MDA-MB-134-VI cells, into the mouse milk ducts. Using patient-derived intraductal xenografts from lobular and non-lobular ER <sup>+</sup> HER2 <sup>-</sup> tumors to compare global gene expression, we identify extracellular matrix modulation as a lobular carcinoma cell-intrinsic trait. Analysis of TCGA patient datasets shows matrisome signature is enriched in lobular carcinomas with overexpression of elastin, collagens, and the collagen modifying enzyme LOXL1. Treatment with the pan LOX inhibitor BAPN and silencing of LOXL1 expression decrease tumor growth, invasion, and metastasis by disrupting ECM structure resulting in decreased ER signaling. We conclude that LOXL1 inhibition is a promising therapeutic strategy for ILC.
Mots-clé
LOXL1, extracellular matrix, lobular carcinoma, preclinical models, xenografts
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/09/2021 16:21
Dernière modification de la notice
12/01/2022 8:11
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