Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects

Authors

Kaitlin Garofano, Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Vera Mariani, Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Kameron Rashid, Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Sumanun Suwunnakorn, Department of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Alfateh Sidahmed, Department of Medicine, George Washington University, Washington, DC, USA.
Anelia Horvath, Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC, USA.
Sanjay B. Maggirwar, Department of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USA.
Travis J. O'Brien, Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Minoli A. Perera, Department of Pharmacology and Center for Pharmacogenomics, Northwestern University, Chicago, IL, USAand.
Michael Whalen, GW Cancer Center, George Washington University, Washington, DC, USA.
Norman H. Lee, Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.

Document Type

Journal Article

Publication Date

12-1-2025

Journal

Platelets

Volume

36

Issue

1

DOI

10.1080/09537104.2024.2449344

Keywords

Apoptosis; MDA-PCa-2b cells; RC77T/E cells; cancer biology; cell invasion; functional genomics; platelet; platelet-like particle; prostate cancer

Abstract

Platelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs. Functionally, PLPs do not aggregate following epinephrine, collagen, or ADP stimulation. While PLPs aggregated in response to thrombin, they did not display enhanced expression of surface markers P-selectin and activated αβ, in contrast to platelets. We have previously demonstrated that platelets physically couple to MDA-PCa-2b and RC77T/E prostate cancer (PCa) cells via specific ligand-receptor interactions, leading to platelet-stimulated cell invasiveness and apoptotic resistance, and reciprocal cell-induced platelet aggregation. In contrast, PLP interactions with PCa cells inhibited both cell invasion and apoptotic resistance while failing to promote PLP aggregation. Moreover, PLPs reduced platelet-PCa cell interactions and antagonized platelet-stimulated oncogenic effects in PCa cells. RNA-Seq analysis identified candidate ligand-transmembrane protein combinations involved in anti-tumorigenic signaling of PLPs to PCa cells. Antibody neutralization of the TIMP3-MMP15 and VEGFB-FGFR1 signaling axes reversed PLP-mediated anti-invasion and apoptotic sensitization, respectively. In summary, PLPs lack many transcriptomic, molecular and functional features of platelets and possess novel anti-tumorigenic properties. These findings indicate that PLPs may have a potential therapeutic role in targeting and disrupting the oncogenic signaling between platelets and cancer cells, offering a new avenue for anti-cancer strategies.

APA Citation

Garofano, Kaitlin; Mariani, Vera; Rashid, Kameron; Suwunnakorn, Sumanun; Sidahmed, Alfateh; Horvath, Anelia; Maggirwar, Sanjay B.; O'Brien, Travis J.; Perera, Minoli A.; Whalen, Michael; and Lee, Norman H., "Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects" (2025). GW Authored Works. Paper 6286.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6286

Department

Pharmacology and Physiology