ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion
Rattachement africain : dk, fi, it. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Macrophages in the tumor microenvironment have a substantial impact on tumor progression. Depending on the signaling environment in the tumor, macrophages can either support or constrain tumor progression. It is therefore of therapeutic interest to identify the tumor-derived factors that control macrophage education. With this aim, we correlated the expression of A Disintegrin and Metalloproteinase (ADAM) proteases, which are key mediators of cell-cell signaling, to the expression of protumorigenic macrophage markers in human cancer cohorts. We identified ADAM17, a sheddase upregulated in many cancer types, as a protein of interest. Depletion of ADAM17 in cancer cell lines reduced the expression of several protumorigenic markers in neighboring macrophages in vitro as well as in mouse models. Moreover, ADAM17-/- educated macrophages demonstrated a reduced ability to induce cancer cell invasion. Using mass spectrometry-based proteomics and ELISA, we identified heparin-binding EGF (HB-EGF) and amphiregulin, shed by ADAM17 in the cancer cells, as the implicated molecular mediators of macrophage education. Additionally, RNA-Seq and ELISA experiments revealed that ADAM17-dependent HB-EGF ligand release induced the expression and secretion of CXCL chemokines in macrophages, which in turn stimulated cancer cell invasion. In conclusion, we provide evidence that ADAM17 mediates a paracrine EGFR-ligand-chemokine feedback loop, whereby cancer cells hijack macrophages to promote tumor progression.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- ADAM17-mediated EGFR ligand shedding directs macrophage-promoted cancer cell invasion
- Date Crossref
- 22/09/2022
- Éditeur
- American Society for Clinical Investigation
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Copenhagen Biotech Research and Innovation Centre (BRIC) pays non établi dans la noticeUniversité ou école supérieure
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Technical University of Denmark Department of Biotechnology and Biomedicine pays non établi dans la noticeUniversité ou école supérieure
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Copenhagen University Hospital Department of Oncology pays non établi dans la noticeÉtablissement de santé
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University of Turku Department of Pathology pays non établi dans la noticeUniversité ou école supérieure
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Institute for Biomedicine pays non établi dans la noticeStructure de recherche
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Institute of Biomedicine and pays non établi dans la noticeStructure de recherche
Biotech Research and Innovation Centre (BRIC) — University of Copenhagen, Department of Biotechnology and Biomedicine — Technical University of Denmark et Department of Oncology — Copenhagen University Hospital, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.