Skip to Main content Skip to Navigation
Journal articles

ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis

Abstract : The transmembrane metalloprotease-disintegrin ADAM8 mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components. Here, we report that ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs). Furthermore, high ADAM8 levels predicted poor patient outcome. Consistently, ADAM8 promoted an aggressive phenotype of TNBC cells in culture. In a mouse orthotopic model, tumors derived from TNBC cells with ADAM8 knockdown failed to grow beyond a palpable size and displayed poor vascularization. Circulating tumor cells and brain metastases were also significantly reduced. Mechanisti-cally, ADAM8 stimulated both angiogenesis through release of VEGF-A and transendothelial cell migration via β1-integrin activation. In vivo, treatment with an anti-ADAM8 antibody from the time of cell inoculation reduced primary tumor burden and metastases. Furthermore, antibody treatment of established tumors profoundly decreased metastases in a resection model. As a non-essential protein under physiological conditions, ADAM8 represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination.
Document type :
Journal articles
Complete list of metadatas

Cited literature [50 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02447040
Contributor : Sophie Barillé-Nion <>
Submitted on : Tuesday, January 21, 2020 - 12:25:37 PM
Last modification on : Friday, June 19, 2020 - 3:08:56 AM
Document(s) archivé(s) le : Wednesday, April 22, 2020 - 5:52:10 PM

File

emmm.201303373.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Mathilde Romagnoli, Nora Mineva, Michael Polmear, Catharina Conrad, Srimathi Srinivasan, et al.. ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis. EMBO Molecular Medicine, Wiley Open Access, 2014, 6 (2), pp.278-294. ⟨10.1002/emmm.201303373⟩. ⟨inserm-02447040⟩

Share

Metrics

Record views

103

Files downloads

111