Drug Resistance: The Role of Exosomal MiRNA in the Microenvironment of Hematopoietic Tumors

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Jan 8

PMID 36615316

Authors

Mariaconcetta Cariello

Angela Squilla

Martina Piacente

Giorgia Venutolo

Alessio Fasano

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs), including exosomes, have an important role thanks to their ability to communicate and exchange information between tumor cells and the tumor microenvironment (TME), and have also been associated with communicating anti-cancer drug resistance (DR). The increase in proliferation of cancer cells alters oxygen levels, which causes hypoxia and results in a release of exosomes by the cancer cells. In this review, the results of studies examining the role of exosomal miRNA in DR, and their mechanism, are discussed in detail in hematological tumors: leukemia, lymphoma, and multiple myeloma. In conclusion, we underline the exosome's function as a possible drug delivery vehicle by understanding its cargo. Engineered exosomes can be used to be more specific for personalized therapy.

Citing Articles

Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.

Khattab S, Berisha A, Baran N, Piccaluga P Biomedicines. 2025; 13(1).

PMID: 39857784 PMC: 11760468. DOI: 10.3390/biomedicines13010202.

Immune checkpoints and ncRNAs: pioneering immunotherapy approaches for hematological malignancies.

Anvari S, Nikbakht M, Vaezi M, Amini-Kafiabad S, Ahmadvand M Cancer Cell Int. 2024; 24(1):410.

PMID: 39702293 PMC: 11660508. DOI: 10.1186/s12935-024-03596-8.

Potential Use of Exosomal Non-Coding MicroRNAs in Leukemia Therapy: A Systematic Review.

Gil-Kulik P, Kluz N, Przywara D, Petniak A, Wasilewska M, Fraczek-Chudzik N Cancers (Basel). 2024; 16(23).

PMID: 39682135 PMC: 11639955. DOI: 10.3390/cancers16233948.

Recent Progress of Exosomes in Hematological Malignancies: Pathogenesis, Diagnosis, and Therapeutic Strategies.

Zhang H, Xia J, Wang X, Wang Y, Chen J, He L Int J Nanomedicine. 2024; 19:11611-11631.

PMID: 39539968 PMC: 11559222. DOI: 10.2147/IJN.S479697.

Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies.

Olejarz W, Sadowski K, Szulczyk D, Basak G Int J Mol Sci. 2024; 25(14).

PMID: 39062986 PMC: 11276786. DOI: 10.3390/ijms25147743.

References

Hu S, Ma J, Su C, Chen Y, Shu Y, Qi Z . Engineered exosome-like nanovesicles suppress tumor growth by reprogramming tumor microenvironment and promoting tumor ferroptosis. Acta Biomater. 2021; 135:567-581. DOI: 10.1016/j.actbio.2021.09.003. View

Deep G, Panigrahi G . Hypoxia-Induced Signaling Promotes Prostate Cancer Progression: Exosomes Role as Messenger of Hypoxic Response in Tumor Microenvironment. Crit Rev Oncog. 2016; 20(5-6):419-34. PMC: 5308872. DOI: 10.1615/CritRevOncog.v20.i5-6.130. View

Shao C, Yang F, Miao S, Liu W, Wang C, Shu Y . Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018; 17(1):120. PMC: 6087002. DOI: 10.1186/s12943-018-0869-y. View

Min Q, Wang X, Zhang J, Chen Q, Li S, Liu X . Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365. Exp Cell Res. 2017; 362(2):386-393. DOI: 10.1016/j.yexcr.2017.12.001. View

Wang Y, Liu Q, Wang F . Potential roles of exosome non‑coding RNAs in cancer chemoresistance (Review). Oncol Rep. 2021; 45(2):439-447. PMC: 7757100. DOI: 10.3892/or.2020.7887. View

Li Q, Zhang D, Wang Y, Sun P, Hou X, Larner J . MiR-21/Smad 7 signaling determines TGF-β1-induced CAF formation. Sci Rep. 2013; 3:2038. PMC: 3687228. DOI: 10.1038/srep02038. View

Wang D, Zhao C, Xu F, Zhang A, Jin M, Zhang K . Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics. 2021; 11(6):2860-2875. PMC: 7806469. DOI: 10.7150/thno.51797. View

Shain K, Dalton W, Tao J . The tumor microenvironment shapes hallmarks of mature B-cell malignancies. Oncogene. 2015; 34(36):4673-82. PMC: 4688902. DOI: 10.1038/onc.2014.403. View

Litwinska Z, Luczkowska K, Machalinski B . Extracellular vesicles in hematological malignancies. Leuk Lymphoma. 2018; 60(1):29-36. DOI: 10.1080/10428194.2018.1459606. View

10.

Chen S, Yang X, Feng W, Liao J, Wang L, Feng L . Organ-specific microenvironment modifies diverse functional and phenotypic characteristics of leukemia-associated macrophages in mouse T cell acute lymphoblastic leukemia. J Immunol. 2015; 194(6):2919-29. DOI: 10.4049/jimmunol.1400451. View

11.

Sharma A . Chemoresistance in cancer cells: exosomes as potential regulators of therapeutic tumor heterogeneity. Nanomedicine (Lond). 2017; 12(17):2137-2148. DOI: 10.2217/nnm-2017-0184. View

12.

Bebelman M, Smit M, Pegtel D, Baglio S . Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018; 188:1-11. DOI: 10.1016/j.pharmthera.2018.02.013. View

13.

Moller A, Lobb R . The evolving translational potential of small extracellular vesicles in cancer. Nat Rev Cancer. 2020; 20(12):697-709. DOI: 10.1038/s41568-020-00299-w. View

14.

Anderson K, Carrasco R . Pathogenesis of myeloma. Annu Rev Pathol. 2011; 6:249-74. DOI: 10.1146/annurev-pathol-011110-130249. View

15.

Ostrowski M, Carmo N, Krumeich S, Fanget I, Raposo G, Savina A . Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2009; 12(1):19-30. DOI: 10.1038/ncb2000. View

16.

Jaiswal R, Luk F, Gong J, Mathys J, Grau G, Bebawy M . Microparticle conferred microRNA profiles--implications in the transfer and dominance of cancer traits. Mol Cancer. 2012; 11:37. PMC: 3499176. DOI: 10.1186/1476-4598-11-37. View

17.

Vinay D, Ryan E, Pawelec G, Talib W, Stagg J, Elkord E . Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015; 35 Suppl:S185-S198. DOI: 10.1016/j.semcancer.2015.03.004. View

18.

Tajima F, Kawatani T, Endo A, Kawasaki H . Natural killer cell activity and cytokine production as prognostic factors in adult acute leukemia. Leukemia. 1996; 10(3):478-82. View

19.

Zhang H, Deng T, Liu R, Ning T, Yang H, Liu D . CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer. Mol Cancer. 2020; 19(1):43. PMC: 7045485. DOI: 10.1186/s12943-020-01168-8. View

20.

Horiguchi H, Kobune M, Kikuchi S, Yoshida M, Murata M, Murase K . Extracellular vesicle miR-7977 is involved in hematopoietic dysfunction of mesenchymal stromal cells via poly(rC) binding protein 1 reduction in myeloid neoplasms. Haematologica. 2016; 101(4):437-47. PMC: 5004399. DOI: 10.3324/haematol.2015.134932. View