Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells
Abstract
:1. Introduction
2. Results
2.1. Distinct Response of U251 and LN428 to Resveratrol
2.2. Prepared Exosomes from U251 and LN428 Cells without and with Drug Treatment
2.3. U251/N/Exo but Not U251/Res/Exo Reversed Resveratrol Resistance of LN428 Cells
2.4. Distinct Protein Compositions of U251- and LN428-Derived Exosomes
2.5. Functional Classification of U251- and LN428-Derived Exosomic Proteins
2.6. Differential Functional Enrichment in U251/N/Exo and U251/Res/Exo
2.7. Proteomic Similarities of LN428/N/Exo and LN428/Res/Exo
3. Discussion
4. Materials and Methods
4.1. Glioblastoma Multiform (GBM) Cell Lines and Culture
4.2. Resveratrol Treatment and Cell Response
4.3. Evaluation of Cell Proliferation and Death
4.4. Sample Preparation and Exosome Isolation
4.5. Transmission Electron Microscopy-Based Exosome Identification
4.6. Nanoparticle Tracking Analysis (NTA)-Based Exosome Quantification
4.7. Protein Preparation and Western Blotting
4.8. Exosome Pre-Incubation and Resveratrol Treatment
4.9. Trypsin Digestion and Desalting
4.10. Liquid Chromatography-Mass Spectrometry (LC-MS/MS) Analysis
4.11. Database Search and Bioinformatic Analyses
4.12. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Ostrom, Q.T.; Gittleman, H.; Liao, P.; Vecchione-Koval, T.; Wolinsky, Y.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro Oncol. 2017, 19, v1–v88. [Google Scholar] [CrossRef] [PubMed]
- Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef] [PubMed]
- Weller, M.; van den Bent, M.; Hopkins, K.; Tonn, J.C.; Stupp, R.; Falini, A.; Cohen-Jonathan-Moyal, E.; Frappaz, D.; Henriksson, R.; Balana, C.; et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014, 15, e395–e403. [Google Scholar] [CrossRef] [Green Version]
- Stepanovic, A.; Nikitovic, M. Severe hematologic temozolomide-related toxicity and lifethreatening infections. J. BUON 2018, 23, 7–13. [Google Scholar] [PubMed]
- Bae, S.H.; Park, M.J.; Lee, M.M.; Kim, T.M.; Lee, S.H.; Cho, S.Y.; Kim, Y.H.; Kim, Y.J.; Park, C.K.; Kim, C.Y. Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea. J. Korean Med. Sci. 2014, 29, 980–984. [Google Scholar] [CrossRef] [PubMed]
- Athar, M.; Back, J.H.; Kopelovich, L.; Bickers, D.R.; Kim, A.L. Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch. Biochem. Biophys. 2009, 486, 95–102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Q.; Xu, J.; Rottinghaus, G.E.; Simonyi, A.; Lubahn, D.; Sun, G.Y.; Sun, A.Y. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. 2002, 958, 439–447. [Google Scholar] [CrossRef]
- Gambini, J.; Ingles, M.; Olaso, G.; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K.M.; Gomez-Cabrera, M.C.; Vina, J.; et al. Properties of resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid. Med. Cell. Longev. 2015, 2015, 837042. [Google Scholar] [CrossRef]
- Boocock, D.J.; Faust, G.E.; Patel, K.R.; Schinas, A.M.; Brown, V.A.; Ducharme, M.P.; Booth, T.D.; Crowell, J.A.; Perloff, M.; Gescher, A.J.; et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol. Biomark. Prev. 2007, 16, 1246–1252. [Google Scholar] [CrossRef]
- Juan, M.E.; Maijo, M.; Planas, J.M. Quantification of trans-resveratrol and its metabolites in rat plasma and tissues by HPLC. J. Pharm. Biomed. Anal. 2010, 51, 391–398. [Google Scholar] [CrossRef]
- Pistollato, F.; Bremer-Hoffmann, S.; Basso, G.; Cano, S.S.; Elio, I.; Vergara, M.M.; Giampieri, F.; Battino, M. Targeting glioblastoma with the use of phytocompounds and nanoparticles. Target. Oncol. 2016, 11, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Xue, S.; Shu, X.-H.; Lin, S.; Jie, B.; Wang, L.-L.; Gu, J.-Y.; Shun, S.; Li, P.-N.; Wu, M.-L.; Qian, W.; et al. Lumbar puncture-administered resveratrol inhibits STAT3 activation, enhancing autophagy and apoptosis in orthotopic rat glioblastomas. Oncotarget 2016, 7, 75790–75799. [Google Scholar] [CrossRef] [PubMed]
- Song, X.; Shu, X.H.; Wu, M.L.; Zheng, X.; Jia, B.; Kong, Q.Y.; Liu, J.; Li, H. Postoperative resveratrol administration improves prognosis of rat orthotopic glioblastomas. BMC Cancer 2018, 18, 871. [Google Scholar] [CrossRef] [PubMed]
- Sun, Z.; Li, H.; Shu, X.H.; Shi, H.; Chen, X.Y.; Kong, Q.Y.; Wu, M.L.; Liu, J. Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells. FEBS J. 2012, 279, 2381–2392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, H.; Jia, Z.; Li, A.; Jenkins, G.; Yang, X.; Hu, J.; Guo, W. Resveratrol repressed viability of U251 cells by miR-21 inhibiting of NF-kappaB pathway. Mol. Cell. Biochem. 2013, 382, 137–143. [Google Scholar] [CrossRef]
- Yang, J.K.; Yang, J.P.; Tong, J.; Jing, S.Y.; Fan, B.; Wang, F.; Sun, G.Z.; Jiao, B.H. Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma. J. Neuro-Oncol. 2017, 131, 255–265. [Google Scholar] [CrossRef] [PubMed]
- Fevre-Montange, M.; Champier, J.; Szathmari, A.; Wierinckx, A.; Mottolese, C.; Guyotat, J.; Figarella-Branger, D.; Jouvet, A.; Lachuer, J. Microarray analysis reveals differential gene expression patterns in tumors of the pineal region. J. Neuropathol. Exp. Neurol. 2006, 65, 675–684. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.P.; Xiong, M.; Xu, C.S.; Duan, L.N.; Dong, Y.Q.; Luo, Y.; Niu, T.H.; Lu, C.R. Resveratrol induces apoptosis of human chronic myelogenous leukemia cells in vitro through p38 and JNK-regulated H2AX phosphorylation. Acta Pharmacol. Sin. 2015, 36, 353–361. [Google Scholar] [CrossRef] [Green Version]
- Pasupuleti, N.; Leon, L.; Carraway, K.L., III; Gorin, F. 5-Benzylglycinyl-amiloride kills proliferating and nonproliferating malignant glioma cells through caspase-independent necroptosis mediated by apoptosis-inducing factor. J. Pharmacol. Exp. Ther. 2013, 344, 600–615. [Google Scholar] [CrossRef]
- Arcella, A.; Oliva, M.A.; Staffieri, S.; Aalberti, S.; Grillea, G.; Madonna, M.; Bartolo, M.; Pavone, L.; Giangaspero, F.; Cantore, G.; et al. In vitro and in vivo effect of human lactoferrin on glioblastoma growth. J. Neurosurg. 2015, 123, 1026–1035. [Google Scholar] [CrossRef] [Green Version]
- Li, F.; Cheng, Y.; Lu, J.; Hu, R.; Wan, Q.; Feng, H. Photodynamic therapy boosts anti-glioma immunity in mice: A dependence on the activities of T cells and complement C3. J. Cell. Biochem. 2011, 112, 3035–3043. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Xu, C.; Ding, B.; Gao, M.; Wei, X.; Ji, N. Long non-coding RNA MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101. J. Neuro-Oncol. 2017, 134, 19–28. [Google Scholar] [CrossRef] [PubMed]
- Jovcevska, I.; Zupanec, N.; Urlep, Z.; Vranic, A.; Matos, B.; Stokin, C.L.; Muyldermans, S.; Myers, M.P.; Buzdin, A.A.; Petrov, I.; et al. Differentially expressed proteins in glioblastoma multiforme identified with a nanobody-based anti-proteome approach and confirmed by OncoFinder as possible tumor-class predictive biomarker candidates. Oncotarget 2017, 8, 44141–44158. [Google Scholar] [CrossRef] [PubMed]
- Cherry, A.E.; Stella, N. G protein-coupled receptors as oncogenic signals in glioma: Emerging therapeutic avenues. Neuroscience 2014, 278, 222–236. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, J.; Liu, Y.; Cho, K.; Dong, X.; Teng, L.; Han, D.; Liu, H.; Chen, X.; Chen, X.; Hou, X.; et al. Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming. Neuroreport 2016, 27, 136–144. [Google Scholar] [CrossRef] [PubMed]
- Canella, A.; Welker, A.M.; Yoo, J.Y.; Xu, J.; Abas, F.S.; Kesanakurti, D.; Nagarajan, P.; Beattie, C.E.; Sulman, E.P.; Liu, J.; et al. Efficacy of onalespib, a long-acting second-generation HSP90 inhibitor, as a single agent and in combination with temozolomide against malignant gliomas. Clin. Cancer Res. 2017, 23, 6215–6226. [Google Scholar] [CrossRef]
- Westphal, M.; Heese, O.; Steinbach, J.P.; Schnell, O.; Schackert, G.; Mehdorn, M.; Schulz, D.; Simon, M.; Schlegel, U.; Senft, C.; et al. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur. J. Cancer 2015, 51, 522–532. [Google Scholar] [CrossRef]
- Rehman, A.A.; Elmore, K.B.; Mattei, T.A. The effects of alternating electric fields in glioblastoma: Current evidence on therapeutic mechanisms and clinical outcomes. Neurosurg. Focus 2015, 38, E14. [Google Scholar] [CrossRef]
- Jiao, Y.; Li, H.; Liu, Y.; Guo, A.; Xu, X.; Qu, X.; Wang, S.; Zhao, J.; Li, Y.; Cao, Y. Resveratrol inhibits the invasion of glioblastoma-initiating cells via down-regulation of the PI3K/Akt/NF-kappaB signaling pathway. Nutrients 2015, 7, 4383–4402. [Google Scholar] [CrossRef]
- Song, Z.; Pan, Y.; Ling, G.; Wang, S.; Huang, M.; Jiang, X.; Ke, Y. Escape of U251 glioma cells from temozolomide-induced senescence was modulated by CDK1/survivin signaling. Am. J. Transl. Res. 2017, 9, 2163–2180. [Google Scholar]
- Ishii, N.; Maier, D.; Merlo, A.; Tada, M.; Sawamura, Y.; Diserens, A.C.; Van Meir, E.G. Frequent co-alterations of TP53, p16/CDKN2A, p14ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 1999, 9, 469–479. [Google Scholar] [CrossRef] [PubMed]
- Tang, J.B.; Svilar, D.; Trivedi, R.N.; Wang, X.H.; Goellner, E.M.; Moore, B.; Hamilton, R.L.; Banze, L.A.; Brown, A.R.; Sobol, R.W. N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide. Neuro Oncol. 2011, 13, 471–486. [Google Scholar] [CrossRef] [PubMed]
- Shao, Y.; Shen, Y.; Chen, T.; Xu, F.; Chen, X.; Zheng, S. The functions and clinical applications of tumor-derived exosomes. Oncotarget 2016, 7, 60736–60751. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Challagundla, K.B.; Wise, P.M.; Neviani, P.; Chava, H.; Murtadha, M.; Xu, T.; Kennedy, R.; Ivan, C.; Zhang, X.; Vannini, I.; et al. Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J. Natl. Cancer Inst. 2015, 107. [Google Scholar] [CrossRef] [PubMed]
- Pink, R.C.; Samuel, P.; Massa, D.; Caley, D.P.; Brooks, S.A.; Carter, D.R. The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol. Oncol. 2015, 137, 143–151. [Google Scholar] [CrossRef] [PubMed]
- Azmi, A.S.; Bao, B.; Sarkar, F.H. Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev. 2013, 32, 623–642. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Parry, J.A.; Chin, A.; Duensing, S.; Duensing, A. Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to undergo apoptosis. Mol. Cancer 2008, 7, 61. [Google Scholar] [CrossRef] [Green Version]
- Xiao, L.; Lan, X.; Shi, X.; Zhao, K.; Wang, D.; Wang, X.; Li, F.; Huang, H.; Liu, J. Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer. Cell Death Dis. 2017, 8, e2803. [Google Scholar] [CrossRef] [Green Version]
- Tiek, D.M.; Rone, J.D.; Graham, G.T.; Pannkuk, E.L.; Haddad, B.R.; Riggins, R.B. Alterations in cell motility, proliferation, and metabolism in novel models of acquired temozolomide resistant glioblastoma. Sci. Rep. 2018, 8, 7222. [Google Scholar] [CrossRef]
- Woerner, B.M.; Luo, J.; Brown, K.R.; Jackson, E.; Dahiya, S.M.; Mischel, P.; Benovic, J.L.; Piwnica-Worms, D.; Rubin, J.B. Suppression of G-protein-coupled receptor kinase 3 expression is a feature of classical GBM that is required for maximal growth. Mol. Cancer Res. 2012, 10, 156–166. [Google Scholar] [CrossRef]
- Zhang, Y.L.; Wang, R.C.; Cheng, K.; Ring, B.Z.; Su, L. Roles of Rap1 signaling in tumor cell migration and invasion. Cancer Biol. Med. 2017, 14, 90–99. [Google Scholar] [CrossRef] [Green Version]
- Fragkos, M.; Jurvansuu, J.; Beard, P. H2AX is required for cell cycle arrest via the p53/p21 pathway. Mol. Cell. Biol. 2009, 29, 2828–2840. [Google Scholar] [CrossRef]
- Lu, C.; Zhu, F.; Cho, Y.Y.; Tang, F.; Zykova, T.; Ma, W.Y.; Bode, A.M.; Dong, Z. Cell apoptosis: Requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol. Cell 2006, 23, 121–132. [Google Scholar] [CrossRef] [PubMed]
- Quail, D.F.; Joyce, J.A. The microenvironmental landscape of brain tumors. Cancer Cell 2017, 31, 326–341. [Google Scholar] [CrossRef] [PubMed]
- Yu, W.W.; Cao, S.N.; Zang, C.X.; Wang, L.; Yang, H.Y.; Bao, X.Q.; Zhang, D. Heat shock protein 70 suppresses neuroinflammation induced by alpha-synuclein in astrocytes. Mol. Cell. Neurosci. 2018, 86, 58–64. [Google Scholar] [CrossRef] [PubMed]
- Wen, S.; Li, H.; Wu, M.L.; Fan, S.H.; Wang, Q.; Shu, X.H.; Kong, Q.Y.; Chen, X.Y.; Liu, J. Inhibition of NF-kappaB signaling commits resveratrol-treated medulloblastoma cells to apoptosis without neuronal differentiation. J. Neuro-Oncol. 2011, 104, 169–177. [Google Scholar] [CrossRef]
- O’Brien, K.; Lowry, M.C.; Corcoran, C.; Martinez, V.G.; Daly, M.; Rani, S.; Gallagher, W.M.; Radomski, M.W.; MacLeod, R.A.; O’Driscoll, L. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity. Oncotarget 2015, 6, 32774–32789. [Google Scholar] [CrossRef] [Green Version]
- Qu, L.; Ding, J.; Chen, C.; Wu, Z.J.; Liu, B.; Gao, Y.; Chen, W.; Liu, F.; Sun, W.; Li, X.F.; et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 2016, 29, 653–668. [Google Scholar] [CrossRef]
- Santos, T.G.; Martins, V.R.; Hajj, G.N.M. Unconventional secretion of heat shock proteins in cancer. Int. J. Mol. Sci. 2017, 18, 946. [Google Scholar] [CrossRef]
- Akakura, N.; Hoogland, C.; Takada, Y.K.; Saegusa, J.; Ye, X.; Liu, F.T.; Cheung, A.T.; Takada, Y. The COOH-terminal globular domain of fibrinogen gamma chain suppresses angiogenesis and tumor growth. Cancer Res. 2006, 66, 9691–9697. [Google Scholar] [CrossRef]
- Thuringer, D.; Hammann, A.; Benikhlef, N.; Fourmaux, E.; Bouchot, A.; Wettstein, G.; Solary, E.; Garrido, C. Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells. J. Biol. Chem. 2011, 286, 3418–3428. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Ji, Q.; Yang, Y.; Li, Q.; Wang, Z. Exosome: Function and role in cancer metastasis and drug resistance. Technol. Cancer Res. Treat. 2018, 17. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.P.; Chang, Y.L.; Huang, P.I.; Chiou, G.Y.; Tseng, L.M.; Chiou, S.H.; Chen, M.H.; Chen, M.T.; Shih, Y.H.; Chang, C.H.; et al. Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. J. Cell. Physiol. 2012, 227, 976–993. [Google Scholar] [CrossRef] [PubMed]
- Martins, L.A.; Coelho, B.P.; Behr, G.; Pettenuzzo, L.F.; Souza, I.C.; Moreira, J.C.; Borojevic, R.; Gottfried, C.; Guma, F.C. Resveratrol induces pro-oxidant effects and time-dependent resistance to cytotoxicity in activated hepatic stellate cells. Cell Biochem. Biophys. 2014, 68, 247–257. [Google Scholar] [CrossRef] [PubMed]
- Jiang, H.; Zhang, L.; Kuo, J.; Kuo, K.; Gautam, S.C.; Groc, L.; Rodriguez, A.I.; Koubi, D.; Hunter, T.J.; Corcoran, G.B.; et al. Resveratrol-induced apoptotic death in human U251 glioma cells. Mol. Cancer Ther. 2005, 4, 554–561. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bilen, M.A.; Pan, T.; Lee, Y.C.; Lin, S.C.; Yu, G.; Pan, J.; Hawke, D.; Pan, B.F.; Vykoukal, J.; Gray, K.; et al. Proteomics profiling of exosomes from primary mouse osteoblasts under proliferation versus mineralization conditions and characterization of their uptake into prostate cancer cells. J. Proteome Res. 2017, 16, 2709–2728. [Google Scholar] [CrossRef] [PubMed]
Uniprot Accession | Protein | Log2R * | Biological Function | |||||
---|---|---|---|---|---|---|---|---|
U251N/U251R | LN428N/LN428R | U251N/LN428N | U251R/LN428R | U251N/LN428R | U251R/LN428N | |||
Pro-Differentiation | ||||||||
P05783 | KRT18 | ↑↑↑ * (2.74) | ↓↓ (−1.23) | ↑↑ (1.55) | ↓↓↓ * (−2.43) | ↑ (0.31) | ↓↓ (−1.20) | Promotes differentiation [17] |
Tumor-Suppressor | ||||||||
P16104 | H2AX | ↑↑ (1.76) | ↓ (−0.44) | ↑↑ (1.27) | ↓↓ (−1.58) | ↑ (0.18) | ↓ (−0.48) | Promotes apoptosis and necroptosis [18,19] # |
P02788 | LTF | ↑↑↑ * (2.84) | ND | ND | ND | ND | ND | Increases TMZ sensitivity [20] # |
P01024 | C3 | ND | ↑↑↑ * (2.79) | ND | ND | ND | ND | Increases TMZ and photodynamic therapy sensitivity [21] # |
Tumor-Promoting | ||||||||
P61224 | RAP1B | ↓ (−0.94) | ↑↑ (1.75) | ↓↓ (−1.17) | ↑↑ (1.51) | ↑ (0.58) | ↓ (−0.23) | Promotes proliferation and inhibits apoptosis [22] |
meP60709 | ACTB | ↓↓↓ * (−2.15) | ↑ (0.74) | ↓↓ (−1.92) | ↑ (0.93) | ↓↓ (−1.62) | ↑ (0.63) | The same as the above [23] |
Q5JWF2 | GNAS | ↓↓ (−1.10) | ND | ND | ND | ND | ND | The same as the above [24] |
P08754 | GNAI3 | ↓↓ (−1.10) | ND | ND | ND | ND | ND | The same as the above [24] |
Apoptosis and Necroptosis Pathway | ||||||||
Q12931 | TRAP1 | ND | ↑↑ (1.99) | ND | ND | ND | ND | Reduces TMZ sensitivity [25] $ |
Q58FF8 | HSP90AB2P | ND | ↑↑ (1.89) | ND | ND | ND | ND | Reduces TMZ sensitivity [26] $ |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Nie, J.-H.; Li, H.; Wu, M.-L.; Lin, X.-M.; Xiong, L.; Liu, J. Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells. Int. J. Mol. Sci. 2019, 20, 191. https://doi.org/10.3390/ijms20010191
Nie J-H, Li H, Wu M-L, Lin X-M, Xiong L, Liu J. Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells. International Journal of Molecular Sciences. 2019; 20(1):191. https://doi.org/10.3390/ijms20010191
Chicago/Turabian StyleNie, Jun-Hua, Hong Li, Mo-Li Wu, Xiao-Min Lin, Le Xiong, and Jia Liu. 2019. "Differential Exosomic Proteomic Patterns and Their Influence in Resveratrol Sensitivities of Glioblastoma Cells" International Journal of Molecular Sciences 20, no. 1: 191. https://doi.org/10.3390/ijms20010191