| Autor: |
Rachel Evans, Fabian Flores-Borja, Sina Nassiri, Elena Miranda, Katherine Lawler, Anita Grigoriadis, James Monypenny, Cheryl Gillet, Julie Owen, Peter Gordon, Victoria Male, Anthony Cheung, Farzana Noor, Paul Barber, Rebecca Marlow, Erika Francesch-Domenech, Gilbert Fruhwirth, Mario Squadrito, Borivoj Vojnovic, Andrew Tutt, Frederic Festy, Michele De Palma, Tony Ng |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 27, Iss 7, Pp 1967-1978.e4 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.04.076 |
| Popis: |
Summary: Lymphatic vasculature is crucial for metastasis in triple-negative breast cancer (TNBC); however, cellular and molecular drivers controlling lymphovascular metastasis are poorly understood. We define a macrophage-dependent signaling cascade that facilitates metastasis through lymphovascular remodeling. TNBC cells instigate mRNA changes in macrophages, resulting in β4 integrin-dependent adhesion to the lymphovasculature. β4 integrin retains macrophages proximal to lymphatic endothelial cells (LECs), where release of TGF-β1 drives LEC contraction via RhoA activation. Macrophages promote gross architectural changes to lymphovasculature by increasing dilation, hyperpermeability, and disorganization. TGF-β1 drives β4 integrin clustering at the macrophage plasma membrane, further promoting macrophage adhesion and demonstrating the dual functionality of TGF-β1 signaling in this context. β4 integrin-expressing macrophages were identified in human breast tumors, and a combination of vascular-remodeling macrophage gene signature and TGF-β signaling scores correlates with metastasis. We postulate that future clinical strategies for patients with TNBC should target crosstalk between β4 integrin and TGF-β1. : Breast cancer metastasis through lymphatic vessels is associated with poor prognosis. Evans et al. describe β4 integrin-expressing macrophages that regulate lymphatic vessel structure in breast cancer. Macrophage-released TGF-β1 drives lymphatic cell contraction via RhoA activation, culminating in lymphatic hyperpermeability. This study defines a signaling cascade that could be targeted therapeutically. Keywords: lymphovasculature, macrophages, cancer, remodeling, adhesion, contraction, β4 integrin, TGF-β1, RhoA |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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