Evidence map›Paper›PMID 37144446›Full record

ArticleCirculation research2023

Mechanism of Tumor-Platelet Communications in Cancer.

Tejasvi Dudiki, Manoj Veleeparambil, Irina Zhevlakova, Sudipta Biswas, Eric A Klein, Peter Ford, Eugene A Podrez, Tatiana V Byzova

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
9.2field-weighted citation impact, top 1% 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

52 citing papers in PubMed, 60 citations in OpenAlex.

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  16. Vascular Toxicities of Cancer Therapies: 2025 Update.Arteriosclerosis, thrombosis, and vascular biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Tejasvi DudikiDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).ORCID 0000-0002-2844-1946
Manoj VeleeparambilDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).
Irina ZhevlakovaDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).
Sudipta BiswasDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).ORCID 0000-0003-1235-364X
Eric A KleinGlickman Urological and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Education Institute, Cleveland Clinic, OH (E.A.K.).
Peter FordDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).ORCID 0000-0002-7546-3742
Eugene A PodrezDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).
Tatiana V ByzovaDepartments of Neurosciences, Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH (T.D., M.V., I.Z., S.B., P.F., E.A.P., T.V.B.).
Cleveland Clinic Lerner College of Medicine · USTwitter (United States) · USCleveland Clinic · US

Funding

Pathophysiological Activities of Oxidized PhospholipidsR01HL077213 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PODREZ, EUGENE A · 2005 to 2018
$4.5M
Platelets in CancerR01HL142772 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2018 to 2021
$2.6M
NHLBI NIH HHS R01 HL077213NHLBI NIH HHS R01 HL142772
6 · The paper itself

Abstract

backgroundThrombosis is one of the main complications in cancer patients often leading to mortality. However, the mechanisms underlying platelet hyperactivation are poorly understood.

methodsMurine and human platelets were isolated and treated with small extracellular vesicles (sEVs) from various cancer cell lines. The effects of these cancer-sEVs on platelets were evaluated both in vitro and in vivo using various approaches, including the detection of cancer-sEV-specific markers in murine platelets and patient samples, measurement of platelet activation and thrombosis assays. Signaling events induced by cancer-sEVs and leading to platelet activation were identified, and the use of blocking antibodies to prevent thrombosis was demonstrated.

resultsWe demonstrate that platelets very effectively take up sEVs from aggressive cancer cells. The process of uptake is fast, proceeds effectively in circulation in mice, and is mediated by the abundant sEV membrane protein-CD63. The uptake of cancer-sEVs leads to the accumulation of cancer cell-specific RNA in platelets in vitro and in vivo. The human prostate cancer-sEV-specific RNA marker PCA3 is detected in platelets of ~70% of prostate cancer patients. This was markedly reduced after prostatectomy. In vitro studies showed that platelet uptake of cancer-sEVs induces strong platelet activation in a CD63-RPTPα (receptor-like protein tyrosine phosphatase alpha)-dependent manner. In contrast to physiological agonists ADP and thrombin, cancer-sEVs activate platelets via a noncanonical mechanism. Intravital studies demonstrated accelerated thrombosis both in murine tumor models and in mice that received intravenous injections of cancer-sEVs. The prothrombotic effects of cancer-sEVs were rescued by blocking CD63.

conclusionsTumors communicate with platelets by means of sEVs, which deliver cancer markers and activate platelets in a CD63-dependent manner leading to thrombosis. This emphasizes the diagnostic and prognostic value of platelet-associated cancer markers and identifies new pathways for intervention.

Indexed as

Extracellular VesiclesProstatic NeoplasmsThrombosisAnimalsBlood PlateletsHumansMaleMicePlatelet ActivationSignal Transductionbloodcancerplateletssmall extracellular vesiclesthrombosis

Identifiers

PMID37144446
PMCPMC10213120
OpenAlexW4372300762

What OpenQuestion holds

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Registered trials

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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.