Intraductal xenografts show lobular carcinoma cells rely on their own extracellular matrix and LOXL1.
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Embargo End Date
ICR Authors
Authors
Sflomos, G
Battista, L
Aouad, P
De Martino, F
Scabia, V
Stravodimou, A
Ayyanan, A
Ifticene-Treboux, A
RLS,
Bucher, P
Fiche, M
Ambrosini, G
Brisken, C
Battista, L
Aouad, P
De Martino, F
Scabia, V
Stravodimou, A
Ayyanan, A
Ifticene-Treboux, A
RLS,
Bucher, P
Fiche, M
Ambrosini, G
Brisken, C
Document Type
Journal Article
Date
2021-03-05
Date Accepted
2021-01-05
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+ ) 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.
Citation
EMBO molecular medicine, 2021, 13 (3), pp. e13180 - ?
Source Title
Publisher
WILEY
ISSN
1757-4676
eISSN
1757-4684
Collections
Research Team
Endocrine control mechanisms
Endocrine control mechanisms
Endocrine control mechanisms