ArticleClinical & experimental metastasis2008
Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells.
Article in Clinical & experimental metastasis, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation.The Journal of biological chemistry · 2014Trial
- Tumor-associated macrophages in hepatocellular carcinoma: Cellular plasticity and therapy resistance in crosstalk.Journal of pharmaceutical analysis · 2026Review
- Remodeling the sarcoma microenvironment by simultaneous targeting of urokinase-type plasminogen activator receptors and epidermal growth factor receptors to promote antitumor activity.The Journal of pharmacology and experimental therapeutics · 2025Article
- The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.International journal of molecular sciences · 2025Review
- Programmed Death Ligand-1 in Melanoma and Extracellular Vesicles Promotes Local and Regional Immune Suppression through M2-like Macrophage Polarization.The American journal of pathology · 2025Article
- Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma.Expert review of clinical immunology · 2024Review
- Extracellular matrix in skin diseases: The road to new therapies.Journal of advanced research · 2023Review
- The generation, activation, and polarization of monocyte-derived macrophages in human malignancies.Frontiers in immunology · 2023Review
- Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies.Oncoimmunology · 2022Review
- Chemokine Pathways in Cutaneous Melanoma: Their Modulation by Cancer and Exploitation by the Clinician.Cancers · 2021Review
- Plasminogen Activator Urokinase Receptor Implies Immunosuppressive Features and Acts as an Unfavorable Prognostic Biomarker in Glioma.The oncologist · 2021Article
- Tumor-Associated Macrophages: New Horizons for Pituitary Adenoma Researches.Frontiers in endocrinology · 2021Review
- Prognostic value of uPAR expression and angiogenesis in primary and metastatic melanoma.PloS one · 2019Article
- Macrophages in skin melanoma-the key element in melanomagenesis.Oncology letters · 2018Article
- Translational Significance for Tumor Metastasis of Tumor-Associated Macrophages and Epithelial-Mesenchymal Transition.Frontiers in immunology · 2017Review
- The lymphatic system and pancreatic cancer.Cancer letters · 2016Review
- Blood Neutrophil-to-Lymphocyte Ratio Predicts Tumor Recurrence in Patients with Hepatocellular Carcinoma within Milan Criteria after Hepatectomy.Yonsei medical journal · 2016Article
- Article
- Inflammatory cytokines induce vascular endothelial growth factor-C expression in melanoma-associated macrophages and stimulate melanoma lymph node metastasis.Oncology letters · 2014Article
- Potentiation of tumor cell invasion by co-culture with monocytes accompanying enhanced production of matrix metalloproteinase and fibronectin.Clinical & experimental metastasis · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of this study was to investigate whether tumor cells as well as tumor-associated macrophages (TAMs) contribute to the generation of protease activities essential to tumor cell invasiveness, such as matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9), and the urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR). We found that the enhanced invasiveness through Matrigel-coated filters of B16 murine melanoma cells stimulated with IFNgamma was associated with an higher expression of uPAR and MMP-9 in these cells. Moreover, treatment with anti-MMP-9 or anti-uPAR monoclonal antibodies abrogated the increase of invasiveness in IFNgamma-stimulated melanoma cells, suggesting a cooperation of uPA system and MMP-9 in cytokine-stimulated invasiveness. Invasiveness through Matrigel was also enhanced in B16 melanoma cells exposed to a medium conditioned by TAMs, represented in our experimental model by thioglycollate-elicited macrophages co-cultivated with melanoma cells. Macrophages isolated from these co-cultures were found to express higher levels of uPAR and MMP-9 compared to macrophage cultures alone, and the pro-invasive activity of the co-culture-conditioned medium was abrogated by anti-MMP-9 monoclonal antibodies, but not anti-uPAR monoclonal antibodies. Furthermore, the enhanced uPAR and MMP-9 expression in macrophages co-cultivated with tumor cells seems a rather specific phenomenon, generated through a cell-to-cell contact mechanism. On the whole, our data point to a cooperation between tumor cells and macrophages elicited by tumor cells themselves in generating key enzymes essential in the promotion of tumor invasiveness, such as uPAR and MMP-9.
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Registered trials
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.