ArticleCell communication and signaling : CCS2024
Targeting cancer-derived extracellular vesicles by combining CD147 inhibition with tissue factor pathway inhibitor for the management of urothelial cancer cells.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- From cell lines to the clinic: identifying a urinary BlCa-EV signature through comparative proteomics of bladder cancer lysates and extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.Journal of extracellular vesicles · 2025Article
- Association of FANCD2, TFPI, and CD33 genes with prognosis of lung adenocarcinoma: a bioinformatics study.Discover oncology · 2025Article
- A CD147-targeted small-molecule inhibitor potentiates gemcitabine efficacy by triggering ferroptosis in pancreatic ductal adenocarcinoma.Cell reports. Medicine · 2025Article
- Head and neck squamous cell carcinoma-derived extracellular vesicles mediate Ca²⁺-dependent platelet activation and aggregation through tissue factor.Cell communication and signaling : CCS · 2025Article
- Reprogramming of fatty acid metabolism in thyroid cancer: Potential targets and mechanisms.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- CD147 at the crossroads of glycoprotein networks, metabolic reprogramming, and metastatic progression.Frontiers in immunology · 2025Review
- From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry.Biomedicines · 2024Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundExtracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs.
methodsCell culture supernatants from invasive and non-invasive bladder cancer cell lines and urine samples from patients with BLCA were collected. Large, microvesicle-like EVs were isolated using sequential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and flow cytometry. The impact of urinary or cell supernatant-derived EVs on cellular phenotypes was evaluated using cell-based assays following combined treatment with a specific CD147 inhibitor alone or in combination with a tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant protein that can be released by low-molecular-weight heparins.
resultsWe observed that EVs obtained from the urine samples of patients with muscle-invasive BLCA and from the aggressive bladder cancer cell line J82 exhibited higher TF activity and CD147 expression levels than did their non-invasive counterparts. The shedding of GFP-tagged CD147 into isolated vesicles demonstrated that the vesicles originated from plasma cell membranes. EVs originating from invasive cancer cells were found to trigger migration, secretion of matrix metalloproteinases (MMPs), and invasion. The same induction of MMP activity was replicated using EVs obtained from urine samples of patients with invasive BLCA. EVs derived from cancer cell clones overexpressing TF and CD147 were produced in higher quantities and exhibited a higher invasive potential than those from control cancer cells. TFPI interfered with the effect when used in conjunction with the CD147 inhibitor, further suppressing homotypic EV-induced migration, MMP production, and invasion.
conclusionsOur findings suggest that combining a CD147 inhibitor with low molecular weight heparins to induce TFPI release may be a promising therapeutic approach for urothelial cancer management. This combination can potentially suppress the tumor-promoting actions of cancer-derived microvesicle-like EVs, including collective matrix invasion.
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