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Article

Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis

1
Department of Hematology and Oncology, Stavanger University Hospital, 4068 Stavanger, Norway
2
Department of Clinical Science, University of Bergen, 5021 Bergen, Norway
3
Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
4
Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, 4036 Stavanger, Norway
5
Laboratory of Immunology and Transfusion Medicine, Haugesund Hospital, 5528 Haugesund, Norway
*
Author to whom correspondence should be addressed.
Academic Editors: Farrukh Aqil and Ramesh Chandra Gupta
Cancers 2021, 13(8), 1870; https://doi.org/10.3390/cancers13081870
Received: 28 February 2021 / Revised: 8 April 2021 / Accepted: 11 April 2021 / Published: 14 April 2021
(This article belongs to the Special Issue Exosomes in Cancers Therapy)
Activated or apoptotic platelets both shed platelet microparticles that are proven to be internalized by many different cell types, including cancer cells. Here, we have investigated whether platelet microparticles can transfer their contents to the monocytic leukemia cell line THP-1 and if this could change cell activity and resistance to chemotherapy. We show that platelet microparticles were internalized by THP-1 cells and that platelet-associated microRNAs were elevated after a brief co-incubation. Furthermore, differentiation toward macrophages was induced and cell cycle progression, proliferation, and mitochondrial activity were decreased. Co-incubation with platelet microparticles increased chemotherapy resistance, which also was evident in acute myelogenous leukemia cells from patient samples, and it could be explained by the decrease in cell activity. Thus, platelet microparticles may have a role in the evolution of acute myelogenous leukemia and contribute to development of chemotherapy resistance, making them an interesting target for treatment.
The role of platelets in cancer development and progression is increasingly evident, and several platelet–cancer interactions have been discovered, including the uptake of platelet microparticles (PMPs) by cancer cells. PMPs inherit a myriad of proteins and small RNAs from the parental platelets, which in turn can be transferred to cancer cells following internalization. However, the exact effect this may have in acute myelogenous leukemia (AML) is unknown. In this study, we sought to investigate whether PMPs could transfer their contents to the THP-1 cell line and if this could change the biological behavior of the recipient cells. Using acridine orange stained PMPs, we demonstrated that PMPs were internalized by THP-1 cells, which resulted in increased levels of miR-125a, miR-125b, and miR-199. In addition, co-incubation with PMPs protected THP-1 and primary AML cells against daunorubicin-induced cell death. We also showed that PMPs impaired cell growth, partially inhibited cell cycle progression, decreased mitochondrial membrane potential, and induced differentiation toward macrophages in THP-1 cells. Our results suggest that this altering of cell phenotype, in combination with decrease in cell activity may offer resistance to daunorubicin-induced apoptosis, as serum starvation also yielded a lower frequency of dead and apoptotic cells when treated with daunorubicin. View Full-Text
Keywords: acute myelogenous leukemia; platelets; microparticles; apoptosis acute myelogenous leukemia; platelets; microparticles; apoptosis
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MDPI and ACS Style

Cacic, D.; Reikvam, H.; Nordgård, O.; Meyer, P.; Hervig, T. Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis. Cancers 2021, 13, 1870. https://doi.org/10.3390/cancers13081870

AMA Style

Cacic D, Reikvam H, Nordgård O, Meyer P, Hervig T. Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis. Cancers. 2021; 13(8):1870. https://doi.org/10.3390/cancers13081870

Chicago/Turabian Style

Cacic, Daniel, Håkon Reikvam, Oddmund Nordgård, Peter Meyer, and Tor Hervig. 2021. "Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis" Cancers 13, no. 8: 1870. https://doi.org/10.3390/cancers13081870

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