Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Jan 20

PMID 30658414

Citations 22

Authors

Hoi-Hin Kwok

Ziyu Ning

Peony Wing-Chi Chong

Thomas Shek-Kong Wan

Margaret Heung-Ling Ng

Gloria Y F Ho

Mary Sau-Man Ip

David Chi-Leung Lam

Affiliations

Soon will be listed here.

Abstract

Anaplastic lymphoma kinase () translocation is an actionable mutation in lung adenocarcinoma. Nonetheless tumour consists of heterogeneous cell subpopulations with diverse phenotypes and genotypes, and cancer cells can actively release extracellular vesicles (EVs) to modulate the phenotype of other cells in the tumour microenvironment. We hypothesized that EVs derived from a drug-resistant subpopulation of cells could induce drug resistance in recipient cells. We have established -translocated lung adenocarcinoma cell lines and subclones. The subclones have been characterized and the expression of EV-RNAs determined by quantitative polymerase chain reaction. The effects of EV transfer on drug resistance were examined in vitro. Serum EV-RNA was assayed serially in two patients prescribed ALK-tyrosine kinase inhibitor (ALK-TKI) treatment. We demonstrated that the EVs from an ALK-TKI-resistant subclone could induce drug resistance in the originally sensitive subclone. EV-RNA profiling revealed that miRNAs and , and lncRNAs and were differentially expressed in the EVs secreted by the resistant subclones. These circulating EV-RNA levels have been found to correlate with disease progression of -translocated lung adenocarcinoma in patients prescribed ALK-TKI treatment. The results from this study suggest that EVs released by a drug-resistant subpopulation can induce drug resistance in other subpopulations and may sustain intratumoural heterogeneity.

Citing Articles

Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.

Mir R, Baba S, Elfaki I, Algehainy N, Alanazi M, Altemani F J Cancer. 2024; 15(19):6383-6415.

PMID: 39513123 PMC: 11540496. DOI: 10.7150/jca.98426.

MicroRNA-486-3p affects cisplatin resistance in high-grade serous ovarian cancer by regulating TMIGD2: An experimental study.

Wang J, Wu Y Heliyon. 2024; 10(15):e34978.

PMID: 39145009 PMC: 11320304. DOI: 10.1016/j.heliyon.2024.e34978.

The Role of Intracellular and Extracellular Vesicles in the Development of Therapy Resistance in Cancer.

Wilczak M, Surman M, PRZYBYlO M Curr Pharm Des. 2024; 30(35):2765-2784.

PMID: 39113303 DOI: 10.2174/0113816128326325240723051625.

Extracellular vesicles in non-small cell lung cancer stemness and clinical applications.

Pandya P, Al-Qasrawi D, Klinge S, Justilien V Front Immunol. 2024; 15:1369356.

PMID: 38765006 PMC: 11099288. DOI: 10.3389/fimmu.2024.1369356.

Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.

Ao Y, Gao J, Jiang J, Wang H, Wang S, Ding J Mol Ther. 2023; 31(12):3389-3413.

PMID: 37740493 PMC: 10727995. DOI: 10.1016/j.ymthe.2023.09.015.

References

Soda M, Choi Y, Enomoto M, Takada S, Yamashita Y, Ishikawa S . Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007; 448(7153):561-6. DOI: 10.1038/nature05945. View

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob S, Patel T . MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007; 133(2):647-58. PMC: 4285346. DOI: 10.1053/j.gastro.2007.05.022. View

Rosell R, Wei J, Taron M . Circulating MicroRNA Signatures of Tumor-Derived Exosomes for Early Diagnosis of Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2009; 10(1):8-9. DOI: 10.3816/CLC.2009.n.001. View

Gatenby R, Silva A, Gillies R, Frieden B . Adaptive therapy. Cancer Res. 2009; 69(11):4894-903. PMC: 3728826. DOI: 10.1158/0008-5472.CAN-08-3658. View

Croce C . Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009; 10(10):704-14. PMC: 3467096. DOI: 10.1038/nrg2634. View

Valeri N, Gasparini P, Braconi C, Paone A, Lovat F, Fabbri M . MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2). Proc Natl Acad Sci U S A. 2010; 107(49):21098-103. PMC: 3000294. DOI: 10.1073/pnas.1015541107. View

Balaguer F, Moreira L, Lozano J, Link A, Ramirez G, Shen Y . Colorectal cancers with microsatellite instability display unique miRNA profiles. Clin Cancer Res. 2011; 17(19):6239-49. PMC: 3186834. DOI: 10.1158/1078-0432.CCR-11-1424. View

Kasinski A, Slack F . Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011; 11(12):849-64. PMC: 4314215. DOI: 10.1038/nrc3166. View

Song L, Lin C, Gong H, Wang C, Liu L, Wu J . miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. Cell Res. 2012; 23(2):274-89. PMC: 3567829. DOI: 10.1038/cr.2012.174. View

10.

Wang J, Tian X, Han R, Zhang X, Wang X, Shen H . Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer. Oncogene. 2013; 33(9):1181-9. PMC: 3883922. DOI: 10.1038/onc.2013.42. View

11.

Masliah-Planchon J, Pasmant E, Luscan A, Laurendeau I, Ortonne N, Hivelin M . MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis. BMC Genomics. 2013; 14:473. PMC: 3744175. DOI: 10.1186/1471-2164-14-473. View

12.

Gazdar A, Linnoila R, Kurita Y, Oie H, Mulshine J, Clark J . Peripheral airway cell differentiation in human lung cancer cell lines. Cancer Res. 1990; 50(17):5481-7. View

13.

Bavi P, Jehan Z, Bu R, Prabhakaran S, Al-Sanea N, Al-Dayel F . ALK gene amplification is associated with poor prognosis in colorectal carcinoma. Br J Cancer. 2013; 109(10):2735-43. PMC: 3833224. DOI: 10.1038/bjc.2013.641. View

14.

Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, Perez-Hernandez D, Vazquez J, Martin-Cofreces N . Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013; 4:2980. PMC: 3905700. DOI: 10.1038/ncomms3980. View

15.

Zhou W, Fong M, Min Y, Somlo G, Liu L, Palomares M . Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014; 25(4):501-15. PMC: 4016197. DOI: 10.1016/j.ccr.2014.03.007. View

16.

Chen Z, Fillmore C, Hammerman P, Kim C, Wong K . Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014; 14(8):535-46. PMC: 5712844. DOI: 10.1038/nrc3775. View

17.

Wang W, Li J, Zhu W, Gao C, Jiang R, Li W . MicroRNA-21 and the clinical outcomes of various carcinomas: a systematic review and meta-analysis. BMC Cancer. 2014; 14:819. PMC: 4232634. DOI: 10.1186/1471-2407-14-819. View

18.

Melo S, Sugimoto H, OConnell J, Kato N, Villanueva A, Vidal A . Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014; 26(5):707-21. PMC: 4254633. DOI: 10.1016/j.ccell.2014.09.005. View

19.

Lam D, Luo S, Deng W, Kwan J, Rodriguez-Canales J, Cheung A . Oncogenic mutation profiling in new lung cancer and mesothelioma cell lines. Onco Targets Ther. 2015; 8:195-209. PMC: 4303463. DOI: 10.2147/OTT.S71242. View

20.

Zhang L, Zhang S, Yao J, Lowery F, Zhang Q, Huang W . Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature. 2015; 527(7576):100-104. PMC: 4819404. DOI: 10.1038/nature15376. View