Evidence map›Paper›PMID 38360687›Full record

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.

Vijay Kumar Boddu, Piet Zamzow, Mario Wolfgang Kramer, Axel S Merseburger, Sivahari Prasad Gorantla, Matthias Klinger, Lena Cramer, Thorben Sauer, Timo Gemoll, Nikolas von Bubnoff and 2 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 9 citations in OpenAlex.

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  6. Reprogramming of fatty acid metabolism in thyroid cancer: Potential targets and mechanisms.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Vijay Kumar BodduDepartment of Hematology and Oncology, Section for Experimental Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Piet ZamzowDepartment of Hematology and Oncology, Section for Experimental Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Mario Wolfgang KramerDepartment of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Axel S MerseburgerDepartment of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Sivahari Prasad GorantlaDepartment of Hematology and Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Matthias KlingerInstitute of Anatomy, University of Lübeck, Lübeck, Germany.
Lena CramerDepartment of Hematology and Oncology, Section for Experimental Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Thorben SauerDepartment of Surgery, Section for Translational Surgical Oncology and Biobanking, University Hospital Schleswig-Holstein, Lübeck, Germany.
Timo GemollDepartment of Surgery, Section for Translational Surgical Oncology and Biobanking, University Hospital Schleswig-Holstein, Lübeck, Germany.
Nikolas von BubnoffDepartment of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Frank GieselerDepartment of Hematology and Oncology, Section for Experimental Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany.
Masoud DarabiDepartment of Hematology and Oncology, Section for Experimental Oncology, University Hospital Schleswig-Holstein, Lübeck, Germany. masoud.darabiamin@uksh.de.ORCID 0000-0001-6380-272X
University Hospital Schleswig-Holstein · DEUniversitäres Kinderwunschzentrum Lübeck · DEUniversity of Lübeck · DE

Funding

LEO Pharma Investigator-Initiated Studies fund
6 · The paper itself

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.

Indexed as

BasiginCarcinoma, Transitional CellExtracellular VesiclesLipoproteinsUrinary Bladder NeoplasmsCell Line, TumorHumansBasiginBSG protein, humanlipoprotein-associated coagulation inhibitorLipoproteinsBladder carcinomaCD142EMMPRINMicrovesicles

Identifiers

PMID38360687
PMCPMC10870545
OpenAlexW4391840157

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.