Protein Profiling of Extracellular Vesicles Associated With Cisplatin Resistance in Lung Cancer

被引:9
作者
Balbinotti, Helier [1 ]
Cadore, Nathan A. [1 ]
Dutra, Cristine S. [1 ]
da Silva, Edileuza D. [1 ]
Ferreira, Henrique B. [1 ,2 ]
Zaha, Arnaldo [1 ,2 ]
Monteiro, Karina M. [1 ,2 ]
机构
[1] Univ Fed Rio Grande do Sul, Ctr Biotecnol, Lab Genom Estrutural & Func, Porto Alegre, RS, Brazil
[2] Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Biol Mol & Biotecnol, Porto Alegre, RS, Brazil
关键词
Extracellular vesicles; lung cancer; drug resistance; cisplatin; mass spectrometry; EXOSOMES; CHEMOTHERAPY; GROWTH;
D O I
10.21873/anticanres.14563
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: Extracellular vesicles (EVs) can mediate drug resistance within the tumor microenvironment by delivering bioactive molecules, including proteins. Here, we performed a comparative proteomic analysis of EVs secreted by A549 lung cancer cells and their cisplatin-resistant counterparts in order to identify proteins involved in drug resistance. Materials and Methods: Cells were co-cultivated using a transwell system to evaluate EV exchange. EVs were isolated by ultracentrifugation and analyzed using microscopy and nanoparticle tracking. EV proteome was analyzed by mass spectrometry. Results: EV-mediated communication was observed between co-cultured A549 and A549/CDDP cells. EVs isolated from both cells were mainly exosome-like structures. Extracellular matrix components, cell adhesion proteins, complement factors, histones, proteasome subunits and membrane transporters were found enriched in the EVs released by cisplatin-resistant cells. Conclusion: Proteins identified in this work may have a relevant role in modulating the chemosensitivity of the recipient cells and could represent useful biomarkers to monitor cisplatin response in lung cancer.
引用
收藏
页码:5509 / 5516
页数:8
相关论文
共 38 条
[1]   Ticket to a bubble ride: Cargo sorting into exosomes and extracellular vesicles [J].
Anand, Sushma ;
Samuel, Monisha ;
Kumar, Sharad ;
Mathivanan, Suresh .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2019, 1867 (12)
[2]   Role of platelet-derived growth factors in physiology and medicine [J].
Andrae, Johanna ;
Gallini, Radiosa ;
Betsholtz, Christer .
GENES & DEVELOPMENT, 2008, 22 (10) :1276-1312
[3]   Extracellular vesicles shed from gefitinib-resistant nonsmall cell lung cancer regulate the tumor microenvironment [J].
Choi, Do-Young ;
You, Sungyong ;
Jung, Jae Hun ;
Lee, Jae Cheol ;
Rho, Jin Kyung ;
Lee, Kye Young ;
Freeman, Michael R. ;
Kim, Kwang Pyo ;
Kim, Jayoung .
PROTEOMICS, 2014, 14 (16) :1845-1856
[4]   Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines [J].
Damiano, JS ;
Cress, AE ;
Hazlehurst, LA ;
Shtil, AA ;
Dalton, WS .
BLOOD, 1999, 93 (05) :1658-1667
[5]   Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment [J].
Duma, Narjust ;
Santana-Davila, Rafael ;
Molina, Julian R. .
MAYO CLINIC PROCEEDINGS, 2019, 94 (08) :1623-1640
[6]   Extracellular Vesicles: Subcellular Organelles With the Potential to Spread Cancer Resistance [J].
Ender, Fanny ;
Von Bubnoff, Nikolas ;
Gieseler, Frank .
ANTICANCER RESEARCH, 2019, 39 (07) :3395-3404
[7]   MicroRNAs as regulators of cisplatin-resistance in non-small cell lung carcinomas [J].
Fadejeva, Irina ;
Olschewski, Horst ;
Hrzenjak, Andelko .
ONCOTARGET, 2017, 8 (70) :115754-115773
[8]   Cisplatin in the modern era: The backbone of first-line chemotherapy for non-small cell lung cancer [J].
Fennell, D. A. ;
Summers, Y. ;
Cadranel, J. ;
Benepal, T. ;
Christoph, D. C. ;
Lal, R. ;
Das, M. ;
Maxwell, F. ;
Visseren-Grul, C. ;
Ferry, D. .
CANCER TREATMENT REVIEWS, 2016, 44 :42-50
[9]   SLC1A5 Mediates Glutamine Transport Required for Lung Cancer Cell Growth and Survival [J].
Hassanein, Mohamed ;
Hoeksema, Megan D. ;
Shiota, Masakazu ;
Qian, Jun ;
Harris, Bradford K. ;
Chen, Heidi ;
Clark, Jonathan E. ;
Alborn, William E. ;
Eisenberg, Rosana ;
Massion, Pierre P. .
CLINICAL CANCER RESEARCH, 2013, 19 (03) :560-570
[10]   Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources [J].
Huang, Da Wei ;
Sherman, Brad T. ;
Lempicki, Richard A. .
NATURE PROTOCOLS, 2009, 4 (01) :44-57