# Roles of mRNA Transfer in Cancer Cell-Platelet Communication

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2024 · $378,223

## Abstract

The interaction between cancer cells and platelets plays important roles in regulating cancer cell function.
Understanding how platelets communicate with cancer cells to modulate cancer cell colonization at distant
organs may identify novel strategies to halt cancer spreading. We recently showed that recruitment of platelet to
cancer cells is essential for the colonization of circulating tumor cells (CTCs) at the secondary organs. However,
the molecular mechanism by which platelets modulate cancer cell function to promote cancer cell colonization
remains to be determined. By analyzing RNA-seq data from CTCs and primary tumors, we found that platelet-
specific mRNA was significantly enriched in CTCs. RNAscope and Translating Ribosome Affinity Purification
(TRAP) analyses showed the delivery of platelet mRNA and translation of platelet-derived mRNA in cancer cells.
In vivo functional screening identified multiple platelet-derived mRNAs contribute to colonization of breast cancer
cell at distant organs. These results reveal the new role of platelet mRNA in mediating intercellular
communication and in promoting cancer cell spreading. The overall objective of this proposal is to define the
molecular mechanism by which platelet mRNA is delivered into breast cancer cells and determine roles of platelet
mRNA as the signaling molecular in promoting cancer cell colonization at distant organs. We showed that CD9
expression in CTCs correlated with the accumulation of platelet-specific mRNA. Silencing CD9 in breast cancer
cells significantly reduced platelet mRNA transferring and colonization of cancer cells. Platelet factor 4 (PF4) is
a small cytokine belonging to the CXC chemokine family that is highly expressed in platelets. We showed that
the transfer of PF4 mRNA from platelets to breast cancer cells enhanced stemness and colonization of cancer
cells. Based on these results, the central hypothesis of this proposal is that the CD9-dependent mRNA transfer
mediates the platelet-cancer cell communication and promotes cancer cell stemness. We propose the following
two aims to test this hypothesis and achieve our objective. Aim 1. Elucidate the mechanism by which platelet
mRNA is transferred into cancer cells. Aim 2. Determine how the transfer of platelet PF4 mRNA in cancer cells
promotes cancer metastasis.

## Key facts

- **NIH application ID:** 10876989
- **Project number:** 5R01CA277946-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ren Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $378,223
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876989

## Citation

> US National Institutes of Health, RePORTER application 10876989, Roles of mRNA Transfer in Cancer Cell-Platelet Communication (5R01CA277946-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10876989. Licensed CC0.

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