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research article

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

Sflomos, George
•
Battista, Laura  
•
Aouad, Patrick
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February 22, 2021
EMBO Molecular Medicine

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+) 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+ HER2− 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.

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Type
research article
DOI
10.15252/emmm.202013180
Author(s)
Sflomos, George
Battista, Laura  
Aouad, Patrick
De Martino, Fabio  
Scabia, Valentina  
Stravodimou, Athina
Ayyanan, Ayyakkannu  
Ifticene‐Treboux, Assia
Bucher, Philipp  
Fiche, Maryse
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Date Issued

2021-02-22

Published in
EMBO Molecular Medicine
Volume

13

Issue

3

Start page

1

End page

19, e13180

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPBRI  
Available on Infoscience
March 19, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/176049
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