Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects
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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Platelets |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09537104.2024.2449344 |
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| author | Kaitlin Garofano Vera Mariani Kameron Rashid Sumanun Suwunnakorn Alfateh Sidahmed Anelia Horvath Sanjay B. Maggirwar Travis J. O’Brien Minoli A. Perera Michael Whalen Norman H. Lee |
| author_facet | Kaitlin Garofano Vera Mariani Kameron Rashid Sumanun Suwunnakorn Alfateh Sidahmed Anelia Horvath Sanjay B. Maggirwar Travis J. O’Brien Minoli A. Perera Michael Whalen Norman H. Lee |
| author_sort | Kaitlin Garofano |
| collection | DOAJ |
| description | 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 α2bβ3, 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. |
| format | Article |
| id | doaj-art-e9eb6e85a4ae4fbd958ee6fdd84ecc0c |
| institution | Kabale University |
| issn | 0953-7104 1369-1635 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj-art-e9eb6e85a4ae4fbd958ee6fdd84ecc0c2025-01-15T12:23:15ZengTaylor & Francis GroupPlatelets0953-71041369-16352025-12-0136110.1080/09537104.2024.2449344Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effectsKaitlin Garofano0Vera Mariani1Kameron Rashid2Sumanun Suwunnakorn3Alfateh Sidahmed4Anelia Horvath5Sanjay B. Maggirwar6Travis J. O’Brien7Minoli A. Perera8Michael Whalen9Norman H. Lee10Department of Pharmacology and Physiology, George Washington University, Washington, DC, USADepartment of Pharmacology and Physiology, George Washington University, Washington, DC, USADepartment of Pharmacology and Physiology, George Washington University, Washington, DC, USADepartment of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USADepartment of Medicine, George Washington University, Washington, DC, USADepartment of Biochemistry and Molecular Medicine, George Washington University, Washington, DC, USADepartment of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, USADepartment of Pharmacology and Physiology, George Washington University, Washington, DC, USADepartment of Pharmacology and Center for Pharmacogenomics, Northwestern University, Chicago, IL, USAandGW Cancer Center, George Washington University, Washington, DC, USADepartment of Pharmacology and Physiology, George Washington University, Washington, DC, USAPlatelet-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 α2bβ3, 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.https://www.tandfonline.com/doi/10.1080/09537104.2024.2449344Apoptosiscancer biologycell invasionfunctional genomicsMDA-PCa-2b cellsplatelet |
| spellingShingle | Kaitlin Garofano Vera Mariani Kameron Rashid Sumanun Suwunnakorn Alfateh Sidahmed Anelia Horvath Sanjay B. Maggirwar Travis J. O’Brien Minoli A. Perera Michael Whalen Norman H. Lee Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects Platelets Apoptosis cancer biology cell invasion functional genomics MDA-PCa-2b cells platelet |
| title | Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects |
| title_full | Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects |
| title_fullStr | Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects |
| title_full_unstemmed | Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects |
| title_short | Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects |
| title_sort | transcriptomic and functional characterization of megakaryocytic derived platelet like particles impaired aggregation and prominent anti tumor effects |
| topic | Apoptosis cancer biology cell invasion functional genomics MDA-PCa-2b cells platelet |
| url | https://www.tandfonline.com/doi/10.1080/09537104.2024.2449344 |
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