ArticleInternational journal of molecular sciences2022
ADAM8-Dependent Extracellular Signaling in the Tumor Microenvironment Involves Regulated Release of Lipocalin 2 and MMP-9.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 18 citations in OpenAlex.
- Deciphering the regulatory role of ADAM8 in the PDAC tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Exosome crown proteins are promising markers for liquid biopsy of breast cancer.Frontiers in oncology · 2026Review
- Endoplasmic reticulum autophagy in inflammatory diseases.Frontiers in immunology · 2026Review
- The role of ADAM8 in intrahepatic cholangiocarcinoma.Discover oncology · 2025Review
- ADAM8 deficiency in macrophages promotes cardiac repair after myocardial infarction via ANXA2-mTOR-autophagy pathway.Journal of advanced research · 2025Article
- Extracellular Release of a Disintegrin and Metalloproteinase Correlates With Periodontal Disease Severity.Journal of clinical periodontology · 2025Article
- Interferon Regulatory Factor 4 Recruits Immature B Cells to Signal Tertiary Lymphoid Structure Immaturity and Progression of Clear Cell Renal Cell Carcinoma.International journal of biological sciences · 2025Article
- Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism.Neuro-oncology · 2024Article
- Correlation of MR-Based Metabolomics and Molecular Profiling in the Tumor Microenvironment of Temozolomide-Treated Orthotopic GL261 Glioblastoma in Mice.International journal of molecular sciences · 2023Article
- The role of ADAM8 in the mechanophenotype of MDA-MB-231 breast cancer cells in 3D extracellular matrices.Frontiers in cell and developmental biology · 2023Article
- The versatile roles of ADAM8 in cancer cell migration, mechanics, and extracellular matrix remodeling.Frontiers in cell and developmental biology · 2023Review
- Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide.Biomedicines · 2022Article
- (Dis)similarities between the Decidual and Tumor Microenvironment.Biomedicines · 2022Review
- Proteases: Role and Function in Cancer.International journal of molecular sciences · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The metalloprotease-disintegrin ADAM8 is critically involved in the progression of pancreatic cancer. Under malignant conditions, ADAM8 is highly expressed and could play an important role in cell-cell communication as expression has been observed in tumor and immune cells of the tumor microenvironment (TME) such as macrophages. To analyze the potential role of ADAM8 in the TME, ADAM8 knockout PDAC tumor cells were generated, and their release of extracellular vesicles (EVs) was analyzed. In EVs, ADAM8 is present as an active protease and associated with lipocalin 2 (LCN2) and matrix metalloprotease 9 (MMP-9) in an ADAM8-dependent manner, as ADAM8 KO cells show a lower abundance of LCN2 and MMP-9. Sorting of ADAM8 occurs independent of TSG101, even though ADAM8 contains the recognition motif PTAP for the ESCRTI protein TSG101 within the cytoplasmic domain (CD). When tumor cells were co-cultured with macrophages (THP-1 cells), expression of LCN2 and MMP-9 in ADAM8 KO cells was induced, suggesting that macrophage signaling can overcome ADAM8-dependent intracellular signaling in PDAC cells. In co-culture with macrophages, regulation of MMP-9 is independent of the M1/M2 polarization state, whereas LCN2 expression is preferentially affected by M1-like macrophages. From these data, we conclude that ADAM8 has a systemic effect in the tumor microenvironment, and its expression in distinct cell types has to be considered for ADAM8 targeting in tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.