Platelet microparticles influence gene expression and modulate biological activities of chronic myeloid leukemia cells (K562).
Humans
Cell-Derived Microparticles
/ metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ genetics
Blood Platelets
/ metabolism
K562 Cells
Cell Proliferation
/ genetics
Apoptosis
/ genetics
Cell Cycle
/ genetics
bcl-2-Associated X Protein
/ metabolism
Cyclin D1
/ metabolism
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Gene Expression Regulation, Leukemic
Chronic myeloid leukemia
Gene expression
Platelet
Platelet-derived microparticles
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
25 May 2024
25 May 2024
Historique:
received:
11
08
2023
accepted:
26
02
2024
medline:
26
5
2024
pubmed:
26
5
2024
entrez:
25
5
2024
Statut:
epublish
Résumé
The current understanding emphasizes the intricate interplay between the Leukemic cell and its environment. Platelet-derived microparticles play a crucial role in facilitating intercellular communication and contribute to the complex landscape of cancer pathology. This study aimed to investigate the influence of platelet-derived microparticles on cell proliferation, apoptosis, and the expression of key genes, including P53, P21, Cyclin D1, Bax, and Bcl-2, within the context of a chronic myeloid leukemia cell line (K562). Platelet-derived microparticles were obtained through centrifugation at various speeds, and their concentration was quantified using the BCA assay. To determine the size and immunophenotypic characteristics of the PMPs, both the DLS technique and flow cytometry were employed. Cell proliferation was assessed using the MTT assay and hemocytometer, and cell cycle analysis was conducted through DNA content evaluation. Real-time PCR was utilized for gene expression analysis of Bax, Bcl-2, Cyclin D1, P53, and P21. Flow cytometry was employed to examine cell apoptosis. The findings revealed that platelet-derived microparticles have the ability to decrease proliferation of the K562 cell line, while not exerting an impact on apoptosis and cell cycle progression. Analysis through real-time PCR indicated an upregulation in the gene expression of P53, P21, and Bcl-2, accompanied by a downregulation in Bax and Cyclin D1. This investigation sheds light on the intricate relationship between chronic myeloid leukemia and its microenvironment, particularly the involvement of platelet-derived microparticles. The study underscores the potential of platelet-derived microparticles to influence cell behavior and gene expression, providing a deeper understanding of their role in CML and its therapeutic implications.
Sections du résumé
BACKGROUND
BACKGROUND
The current understanding emphasizes the intricate interplay between the Leukemic cell and its environment. Platelet-derived microparticles play a crucial role in facilitating intercellular communication and contribute to the complex landscape of cancer pathology. This study aimed to investigate the influence of platelet-derived microparticles on cell proliferation, apoptosis, and the expression of key genes, including P53, P21, Cyclin D1, Bax, and Bcl-2, within the context of a chronic myeloid leukemia cell line (K562).
METHODS AND RESULTS
RESULTS
Platelet-derived microparticles were obtained through centrifugation at various speeds, and their concentration was quantified using the BCA assay. To determine the size and immunophenotypic characteristics of the PMPs, both the DLS technique and flow cytometry were employed. Cell proliferation was assessed using the MTT assay and hemocytometer, and cell cycle analysis was conducted through DNA content evaluation. Real-time PCR was utilized for gene expression analysis of Bax, Bcl-2, Cyclin D1, P53, and P21. Flow cytometry was employed to examine cell apoptosis. The findings revealed that platelet-derived microparticles have the ability to decrease proliferation of the K562 cell line, while not exerting an impact on apoptosis and cell cycle progression. Analysis through real-time PCR indicated an upregulation in the gene expression of P53, P21, and Bcl-2, accompanied by a downregulation in Bax and Cyclin D1.
CONCLUSION
CONCLUSIONS
This investigation sheds light on the intricate relationship between chronic myeloid leukemia and its microenvironment, particularly the involvement of platelet-derived microparticles. The study underscores the potential of platelet-derived microparticles to influence cell behavior and gene expression, providing a deeper understanding of their role in CML and its therapeutic implications.
Identifiants
pubmed: 38796661
doi: 10.1007/s11033-024-09383-y
pii: 10.1007/s11033-024-09383-y
doi:
Substances chimiques
bcl-2-Associated X Protein
0
Cyclin D1
136601-57-5
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
676Subventions
Organisme : Vice Chancellor for Research and Technology of Kerman University of Medical Sciences
ID : 980010000
Organisme : Vice Chancellor for Research and Technology of Kerman University of Medical Sciences
ID : 980010000
Organisme : Vice Chancellor for Research and Technology of Kerman University of Medical Sciences
ID : 980010000
Organisme : Vice Chancellor for Research and Technology of Kerman University of Medical Sciences
ID : 980010000
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Jabbour E, Kantarjian H (2018) Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 93(3):442–459. https://doi.org/10.1002/ajh.25011
doi: 10.1002/ajh.25011
pubmed: 29411417
Hsieh Y-C, Kirschner K, Copland M (2021) Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia 35(5):1229–1242. https://doi.org/10.1038/s41375-021-01238-w
doi: 10.1038/s41375-021-01238-w
pubmed: 33833387
pmcid: 8102187
Osman AEG, Deininger MW (2021) Chronic myeloid leukemia: modern therapies, current challenges and future directions. Blood Rev 49:100825. https://doi.org/10.1016/j.blre.2021.100825
doi: 10.1016/j.blre.2021.100825
pubmed: 33773846
pmcid: 8563059
Jabbour E, Kantarjian H (2022) Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring. Am J Hematol 97(9):1236–1256. https://doi.org/10.1002/ajh.26642
doi: 10.1002/ajh.26642
pubmed: 35751859
Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP et al (2017) Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 376(10):917–927. https://doi.org/10.1056/NEJMoa1609324
doi: 10.1056/NEJMoa1609324
pubmed: 28273028
pmcid: 5901965
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F et al (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966–984. https://doi.org/10.1038/s41375-020-0776-2
doi: 10.1038/s41375-020-0776-2
pubmed: 32127639
pmcid: 7214240
García-Gutiérrez V, Breccia M, Jabbour E, Mauro M, Cortes JE (2022) A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase. J Hematol Oncol 15(1):90. https://doi.org/10.1186/s13045-022-01309-0
doi: 10.1186/s13045-022-01309-0
pubmed: 35818053
pmcid: 9272596
Repsold L, Pool R, Karodia M, Tintinger G, Joubert AM (2017) An overview of the role of platelets in angiogenesis, apoptosis and autophagy in chronic myeloid leukaemia. Cancer Cell Int 17(1):89. https://doi.org/10.1186/s12935-017-0460-4
doi: 10.1186/s12935-017-0460-4
pubmed: 29118670
pmcid: 5664592
Huong PT, Nguyen LT, Nguyen X-B, Lee SK, Bach D-H (2019) The Role of platelets in the tumor-microenvironment and the drug resistance of cancer cells. Cancers [Internet] 11(2):240
doi: 10.3390/cancers11020240
pubmed: 30791448
Boilard E (2017) Platelet-derived nanomedicine targets cancer. Blood 130(5):561–562. https://doi.org/10.1182/blood-2017-05-786327
doi: 10.1182/blood-2017-05-786327
pubmed: 28775157
Lazar S, Goldfinger LE (2018) Platelet microparticles and miRNA transfer in cancer progression: many targets, modes of action, and effects across cancer stages. Front Cardiovasc Med 5:13. https://doi.org/10.3389/fcvm.2018.00013
doi: 10.3389/fcvm.2018.00013
pubmed: 29564336
pmcid: 5850852
Contursi A, Fullone R, Szklanna-Koszalinska P, Marcone S, Lanuti P, Taus F et al (2023) Tumor-educated platelet extracellular vesicles: proteomic profiling and crosstalk with colorectal cancer cells. Cancers [Internet] 15(2):350
doi: 10.3390/cancers15020350
pubmed: 36672299
Burnouf T, Chou M-L, Lundy DJ, Chuang E-Y, Tseng C-L, Goubran H (2023) Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery. J Biomed Sci 30(1):79. https://doi.org/10.1186/s12929-023-00972-w
doi: 10.1186/s12929-023-00972-w
pubmed: 37704991
pmcid: 10500824
Indana HA, Puspitawati I, Mayasari DS, Hartopo AB (2023) Association of acute hyperglycemia and diabetes mellitus with amount of platelets derived microparticles during acute myocardial infarction. J ASEAN Fed Endocr Soc 38(2):35–40. https://doi.org/10.15605/jafes.038.02.03
doi: 10.15605/jafes.038.02.03
pubmed: 38045660
pmcid: 10692412
Lugo-Gavidia LM, Nolde JM, Carnagarin R, Burger D, Chan J, Robinson S et al (2022) Association of circulating platelet extracellular vesicles and pulse wave velocity with cardiovascular risk estimation. Int J Mol Sci 23(18):10524
doi: 10.3390/ijms231810524
pubmed: 36142436
pmcid: 9505165
Tang Y, Li J, Wang W, Chen B, Chen J, Shen Z et al (2021) Platelet extracellular vesicles enhance the proangiogenic potential of adipose-derived stem cells in vivo and in vitro. Stem Cell Res Ther 12(1):497. https://doi.org/10.1186/s13287-021-02561-w
doi: 10.1186/s13287-021-02561-w
pubmed: 34503551
pmcid: 8427862
Yang Y, Luo H, Liu S, Zhang R, Zhu X, Liu M et al (2019) Platelet microparticles-containing miR-4306 inhibits human monocyte-derived macrophages migration through VEGFA/ERK1/2/NF-κB signaling pathways. Clin Exp Hypertens 41(5):481–491. https://doi.org/10.1080/10641963.2018.1510941
doi: 10.1080/10641963.2018.1510941
pubmed: 30183452
Peterson LF, Lo M-C, Liu Y, Giannola D, Mitrikeska E, Donato NJ et al (2017) Induction of p53 suppresses chronic myeloid leukemia. Leuk Lymphoma 58(9):2165–2175. https://doi.org/10.1080/10428194.2016.1272682
doi: 10.1080/10428194.2016.1272682
Chamani E, Rezaei Z, Dastjerdi K, Javanshir S, Khorsandi K, Mohammadi GA (2020) Evaluation of some genes and proteins involved in apoptosis on human chronic myeloid leukemia cells (K562 cells) by datura innoxia leaves aqueous extract. J Biomol Struct Dyn 38(16):4838–4849. https://doi.org/10.1080/07391102.2019.1691661
doi: 10.1080/07391102.2019.1691661
pubmed: 31709925
Liu W, Zhu X, Tang L, Shen N, Cheng F, Zou P et al (2022) ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway. Sci Rep 12(1):17990. https://doi.org/10.1038/s41598-022-21009-6
doi: 10.1038/s41598-022-21009-6
pubmed: 36289272
pmcid: 9606008
Aatonen MT, Öhman T, Nyman TA, Laitinen S, Grönholm M, Siljander PRM (2014) Isolation and characterization of platelet-derived extracellular vesicles. J Extracell Vesicles 3(1):24692. https://doi.org/10.3402/jev.v3.24692
doi: 10.3402/jev.v3.24692
Zhou M, Feng Y, Zhang X, Chen J, Yao N, Fu S et al (2024) Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells. OncoImmunology 13(1):2304963. https://doi.org/10.1080/2162402X.2024.2304963
doi: 10.1080/2162402X.2024.2304963
pubmed: 38235317
pmcid: 10793703
Liang H, Yan X, Pan Y, Wang Y, Wang N, Li L et al (2015) MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3. Mol Cancer 14(1):58. https://doi.org/10.1186/s12943-015-0327-z
doi: 10.1186/s12943-015-0327-z
pubmed: 25881295
pmcid: 4360939
Ashoub MH, Salavatipour MS, Kasgari FH, Valandani HM, Khalilabadi RM (2023) Extracellular microvesicles: biologic properties, biogenesis, and applications in leukemia. Mol Cell Biochem. https://doi.org/10.1007/s11010-023-04734-y
doi: 10.1007/s11010-023-04734-y
pubmed: 37084166
Rohrbacher M, Hasford J (2009) Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol 22(3):295–302. https://doi.org/10.1016/j.beha.2009.07.007
doi: 10.1016/j.beha.2009.07.007
pubmed: 19959081
Nomura S, Ito T, Satake A, Ishii K (2018) Assessment of soluble cytotoxic T lymphocyte-associated antigen-4, transforming growth factor β1, and platelet-derived microparticles during dasatinib therapy for patients with chronic myelogenous leukemia. J Blood Med 10:1–8. https://doi.org/10.2147/JBM.S187005
doi: 10.2147/JBM.S187005
pubmed: 30588140
pmcid: 6305157
Vismara M, Zarà M, Negri S, Canino J, Canobbio I, Barbieri SS et al (2021) Platelet-derived extracellular vesicles regulate cell cycle progression and cell migration in breast cancer cells. Biochim Biophys Acta (BBA) Mol Cell Res 1868(1):118886. https://doi.org/10.1016/j.bbamcr.2020.118886
doi: 10.1016/j.bbamcr.2020.118886
Capriotti AL, Caruso G, Cavaliere C, Piovesana S, Samperi R, Laganà A (2013) Proteomic characterization of human platelet-derived microparticles. Anal Chim Acta 776:57–63. https://doi.org/10.1016/j.aca.2013.03.023
doi: 10.1016/j.aca.2013.03.023
pubmed: 23601281
Michael JV, Wurtzel JGT, Mao GF, Rao AK, Kolpakov MA, Sabri A et al (2017) Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 130(5):567–580. https://doi.org/10.1182/blood-2016-11-751099
doi: 10.1182/blood-2016-11-751099
pubmed: 28500171
pmcid: 5542851
Gharib E, Veilleux V, Boudreau LH, Pichaud N, Robichaud GA (2023) Platelet-derived microparticles provoke chronic lymphocytic leukemia malignancy through metabolic reprogramming. Front Immunol 14:1207361. https://doi.org/10.3389/fimmu.2023.1207631
doi: 10.3389/fimmu.2023.1207631
Cacic D, Reikvam H, Nordgård O, Meyer P, Hervig T (2021) Platelet microparticles protect acute myelogenous leukemia cells against daunorubicin-induced apoptosis. Cancers [Internet] 13(8):1870
doi: 10.3390/cancers13081870
pubmed: 33919720
Pan Y, Liang H, Liu H, Li D, Chen X, Li L et al (2014) Platelet-secreted MicroRNA-223 promotes endothelial cell apoptosis induced by advanced glycation end products via targeting the insulin-like growth factor 1 receptor. J Immunol 192(1):437–446. https://doi.org/10.4049/jimmunol.1301790
doi: 10.4049/jimmunol.1301790
pubmed: 24307738
Xiao BD, Zhao YJ, Jia XY, Wu J, Wang YG, Huang F (2020) Multifaceted p21 in carcinogenesis, stemness of tumor and tumor therapy. World J Stem Cells 12(6):481–487. https://doi.org/10.4252/wjsc.v12.i6.481
doi: 10.4252/wjsc.v12.i6.481
pubmed: 32742565
pmcid: 7360995
Mello SS, Attardi LD (2018) Deciphering p53 signaling in tumor suppression. Curr Opin Cell Biol 51:65–72. https://doi.org/10.1016/j.ceb.2017.11.005
doi: 10.1016/j.ceb.2017.11.005
pubmed: 29195118
Collier MEW, Ambrose AR, Goodall AH (2022) Does hsa-miR-223-3p from platelet-derived extracellular vesicles regulate tissue factor expression in monocytic cells? Platelets 33(7):1031–1042. https://doi.org/10.1080/09537104.2022.2027903
doi: 10.1080/09537104.2022.2027903
pubmed: 35132909
Szilágyi B, Fejes Z, Rusznyák Á, Fenyvesi F, Pócsi M, Halmi S et al (2021) Platelet microparticles enriched in miR-223 reduce ICAM-1-dependent vascular inflammation in septic conditions. Front Physiol 12:658524. https://doi.org/10.3389/fphys.2021.658524
doi: 10.3389/fphys.2021.658524
pubmed: 34135769
pmcid: 8201999
Lu B, Christensen IT, Ma LW, Wang XL, Jiang LF, Wang CX et al (2018) miR-24-p53 pathway evoked by oxidative stress promotes lens epithelial cell apoptosis in age-related cataracts. Mol Med Rep 17(4):5021–5028. https://doi.org/10.3892/mmr.2018.8492
doi: 10.3892/mmr.2018.8492
pubmed: 29393409
pmcid: 5865963
Pour MSS, Kasgari FH, Farsinejad A, Fatemi A, Hassanshahi G, Khalilabadi RM (2021) Platelet microparticles accelerate proliferation and growth of mesenchymal stem cells through longevity-related genes. Arch Iran Med 24(8):607–614. https://doi.org/10.34172/aim.2021.86
doi: 10.34172/aim.2021.86
Sommer G, Dittmann J, Kuehnert J, Reumann K, Schwartz PE, Will H et al (2011) The RNA-binding protein La contributes to cell proliferation and CCND1 expression. Oncogene 30(4):434–444. https://doi.org/10.1038/onc.2010.425
doi: 10.1038/onc.2010.425
pubmed: 20856207
Liu J-H, Yen C-C, Lin Y-C, Gau J-P, Yang M-H, Chao T-C et al (2004) Overexpression of cyclin D1 in accelerated-phase chronic myeloid leukemia. Leuk Lymphoma 45(12):2419–2425. https://doi.org/10.1080/10428190400003317
doi: 10.1080/10428190400003317
pubmed: 15621754
Baj-Krzyworzeka M, Majka M, Pratico D, Ratajczak J, Vilaire G, Kijowski J et al (2002) Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp Hematol 30(5):450–459. https://doi.org/10.1016/S0301-472X(02)00791-9
doi: 10.1016/S0301-472X(02)00791-9
pubmed: 12031651
Yaftian M, Yari F, Ghasemzadeh M, Fallah Azad V, Haghighi M (2018) Induction of apoptosis in cancer cells of pre-B ALL patients after exposure to platelets, platelet-derived microparticles and soluble CD40 ligand. Cell J 20(1):120–126. https://doi.org/10.22074/cellj.2018.5032
doi: 10.22074/cellj.2018.5032
pubmed: 29308628
pmcid: 5759674
Velez J, Enciso LJ, Suarez M, Fiegl M, Grismaldo A, López C et al (2014) Platelets promote mitochondrial uncoupling and resistance to apoptosis in leukemia cells: a novel paradigm for the bone marrow microenvironment. Cancer Microenviron 7(1):79–90. https://doi.org/10.1007/s12307-014-0149-3
doi: 10.1007/s12307-014-0149-3
pubmed: 25112275
pmcid: 4150878
Bonnefoy-Berard N, Aouacheria A, Verschelde C, Quemeneur L, Marais A, Marvel J (2004) Control of proliferation by Bcl-2 family members. Biochim Biophys Acta (BBA) Mol Cell Res 1644(2):159–68. https://doi.org/10.1016/j.bbamcr.2003.10.014
doi: 10.1016/j.bbamcr.2003.10.014
Nazari M, Javandoost E, Talebi M, Movassaghpour A, Soleimani M (2021) Platelet microparticle controversial role in cancer. Adv Pharm Bull 11(1):39–55. https://doi.org/10.34172/apb.2021.005
doi: 10.34172/apb.2021.005
pubmed: 33747851