# Platelets in Cancer

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $663,334

## Abstract

Abstract
This proposal centers on the mechanisms of cancer-associated thrombosis, also known as
Trousseau's syndrome. In many cancers, platelet-mediated thrombosis is the leading cause of
morbidity. Platelets are present in blood at levels higher than any other cell and their activation and
aggregation leads to thrombosis. Due to the presence of numerous storage granules, platelets are
able to uptake a number of important mediators. Several lines of experimental evidence from our and
other groups suggest that the presence of tumor changes platelet transcriptome, secretome (storage
granules content) as well as platelet activation status resulting in so-called “tumor-educated platelets”.
We have shown that platelets from tumor-bearing mice and platelets from cancer patients carry not
only proteins or tumor origin but also tumor-specific RNAs. To understand how tumor RNAs find their
way to platelets, we focus on vesicles called exosomes, which are produced by aggressive tumors
and contain tumor-specific RNAs and proteins. We demonstrated that tumor exosomes are efficiently
taken in by platelets in vitro and in vivo, resulting in changes of platelet transcriptome and platelet
activation. Capitalizing on these preliminary results we hypothesized that tumor exosomes, containing
tumor signature, are efficiently taken in by platelets via CD63 and platelet secretory granules
machinery (VAMPs). This results in changes in platelet transcriptome and, eventually, in platelet
hyperactivation leading to thrombosis. AIM1. To determine the mechanisms of exosome uptake by
platelets. Using exo from prostate cancer cells and from patients, we will assess the role of CD63 and
its glycosylation in exo uptake by platelets in vitro and in vivo. The role of platelet
endocytosis/exocytosis machinery in exosomes uptake will be tested using VAMP8, VAMP3, Arf6 KO
platelets. AIM2. To define the mechanisms of platelet activation by exo in vivo and identify potential
targets for intervention. Platelet activation by tumors and tumor-derived exo will be monitored in the
presence or absence of CD63 blocking reagents in vivo. AIM3. To define tumor-specific signature in
both, exo and circulating platelets isolated from blood of cancer patients. We will focus on prostate
cancer patients and will measure selected tumor-specific markers in exosomes and platelets by
qPCR. Platelets from patients before and 3 and 6 months after prostatectomy will be assayed for
tumor-specific reporters and activation status. These studies are designed to define the specific
mechanisms and consequences of platelets activation by tumor exosomes and develop new
therapeutic strategies to interfere with cancer-associated thrombosis.

## Key facts

- **NIH application ID:** 10199008
- **Project number:** 5R01HL142772-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Tatiana V Byzova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $663,334
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199008

## Citation

> US National Institutes of Health, RePORTER application 10199008, Platelets in Cancer (5R01HL142772-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199008. Licensed CC0.

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