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

Details

Serval ID
serval:BIB_7FB2372AC0AF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1.
Journal
EMBO molecular medicine
Author(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.
Working group(s)
RLS
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Publication state
Published
Issued date
05/03/2021
Peer-reviewed
Oui
Volume
13
Number
3
Pages
e13180
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
LOXL1, extracellular matrix, lobular carcinoma, preclinical models, xenografts
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2021 16:21
Last modification date
20/09/2021 6:41
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