J Neurol Surg B Skull Base 2024; 85(02): 161-167
DOI: 10.1055/a-2018-4627
Original Article

Investigating the Effects of Chordoma Cell-Derived Exosomes on the Tumorigenicity of Nucleus Pulposus Cells

Esra Aydemir
1   Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, Türkiye
,
Nur Zübeyda Yılmaz
2   Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Türkiye
,
Ömer Faruk Bayrak
3   Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul, Türkiye
,
Fikrettin Sahin
2   Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Türkiye
› Author Affiliations
Funding This study was supported by Yeditepe University research funding.

Abstract

Objective Interaction of tumor cells with the surrounding environment is essential for tumor growth and progression that eventually leads to metastasis. Growing evidence shows that extracellular vesicles also known as exosomes play a crucial role in signaling between the tumor and its microenvironment. Tumor-derived exosomes have generally protumorigenic effects such as metastasis, hypoxia, angiogenesis, and epithelial-mesenchymal transition.

Methods In this study, exosomes were isolated from a chordoma cell line, MUG-Chor1, and characterized subsequently. The number of exosomes was determined and introduced into the healthy nucleus pulposus (NP) cells for 140 days. The protumorigenic effects of a chordoma cell line-derived exosomes that initiate the tumorigenesis on NP cells were investigated. The impact of tumor-derived exosomes on various cellular events including cell cycle, migration, proliferation, apoptosis, and viability has been studied by treating NP cells with chordoma cell-line-derived exosomes cells.

Results Upon treatment with exosomes, the NP cells not only gained a chordoma-like morphology but also molecular characteristics such as alterations in the levels of certain gene expressions. The migratory and angiogenic capabilities of NP cells increased after treatment with chordoma-derived exosomes.

Conclusion Based on our findings, we can conclude that exosomes carry information from tumor cells and may exert tumorigenic effects on nontumorous cells.



Publication History

Received: 05 June 2022

Accepted: 17 January 2023

Accepted Manuscript online:
24 January 2023

Article published online:
24 February 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Bishop JM. Molecular themes in oncogenesis. Cell 1991; 64 (02) 235-248
  • 2 Ellenrieder V, Hendler SF, Boeck W. et al. Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res 2001; 61 (10) 4222-4228
  • 3 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (05) 646-674
  • 4 Anderson ARA, Weaver AM, Cummings PT, Quaranta V. Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. Cell 2006; 127 (05) 905-915
  • 5 Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 2013; 32 (3-4): 623-642
  • 6 Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 2019; 8 (07) 727
  • 7 Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science 2020; 367 (6478): eaau6977
  • 8 Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 2014; 15 (12) 1243-1253
  • 9 Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-mediated metastasis: communication from a distance. Dev Cell 2019; 49 (03) 347-360
  • 10 Whiteside TL. Tumor-derived exosomes and their role in cancer progression. Adv Clin Chem 2016; 74: 103-141
  • 11 Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH. Chordoma: the nonsarcoma primary bone tumor. Oncologist 2007; 12 (11) 1344-1350
  • 12 Bayrak OF, Aydemir E, Gulluoglu S. et al. The effects of chemotherapeutic agents on differentiated chordoma cells. J Neurosurg Spine 2011; 15 (06) 620-624
  • 13 Al-Mefty O. Skull base chordomas. Neurosurg Focus 2001; 10: 1-1
  • 14 Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP. Isolation of extracellular vesicles: general methodologies and latest trends. BioMed Res Int 2018; 2018: 8545347
  • 15 Gao ZW, Wang HP, Lin F. et al. CD73 promotes proliferation and migration of human cervical cancer cells independent of its enzyme activity. BMC Cancer 2017; 17 (01) 135
  • 16 Tratwal J, Follin B, Ekblond A, Kastrup J, Haack-Sørensen M. Identification of a common reference gene pair for qPCR in human mesenchymal stromal cells from different tissue sources treated with VEGF. BMC Mol Biol 2014; 15: 11
  • 17 Coban EA, Kasikci E, Karatas OF. et al. Characterization of stem-like cells in a new astroblastoma cell line. Exp Cell Res 2017; 352 (02) 393-402
  • 18 Liang C-C, Park AY, Guan J-L. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2007; 2 (02) 329-333
  • 19 Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 2014; 14 (03) 195-208
  • 20 Pant S, Hilton H, Burczynski ME. The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol 2012; 83 (11) 1484-1494
  • 21 Wu B, Sun D, Ma L. et al. Exosomes isolated from CAPS1–overexpressing colorectal cancer cells promote cell migration. Oncol Rep 2019; 42 (06) 2528-2536
  • 22 Li K, Chen Y, Li A, Tan C, Liu X. Exosomes play roles in sequential processes of tumor metastasis. Int J Cancer 2019; 144 (07) 1486-1495
  • 23 Fontana S, Saieva L, Taverna S, Alessandro R. Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression: state of the art and new perspectives. Proteomics 2013; 13 (10-11): 1581-1594
  • 24 Johnson WEB, Roberts S. Human intervertebral disc cell morphology and cytoskeletal composition: a preliminary study of regional variations in health and disease. J Anat 2003; 203 (06) 605-612
  • 25 Rinner B, Froehlich EV, Buerger K. et al. Establishment and detailed functional and molecular genetic characterisation of a novel sacral chordoma cell line, MUG-Chor1. Int J Oncol 2012; 40 (02) 443-451
  • 26 Hood JL, Pan H, Lanza GM, Wickline SA. Consortium for Translational Research in Advanced Imaging and Nanomedicine (C-TRAIN). Paracrine induction of endothelium by tumor exosomes. Lab Invest 2009; 89 (11) 1317-1328
  • 27 Hoang DH, Nguyen TD, Nguyen H-P. et al. Differential wound healing capacity of mesenchymal stem cell-derived exosomes originated from bone marrow, adipose tissue and umbilical cord under serum- and Xeno-free condition. Front Mol Biosci 2020; 7: 119
  • 28 Shah SR, David JM, Tippens ND. et al. Brachyury-YAP regulatory axis drives stemness and growth in cancer. Cell Rep 2017; 21 (02) 495-507
  • 29 Chen KW, Yang HL, Lu J, Liu JY, Chen XQ. Prognostic factors of sacral chordoma after surgical therapy: a study of 36 patients. Spinal Cord 2010; 48 (02) 166-171
  • 30 Olejarz W, Kubiak-Tomaszewska G, Chrzanowska A, Lorenc T. Exosomes in angiogenesis and anti-angiogenic therapy in cancers. Int J Mol Sci 2020; 21 (16) 5840
  • 31 Qu L, Ding J, Chen C. et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 2016; 29 (05) 653-668
  • 32 Visconti L, Nelissen K, Deckx L. et al. Prognostic value of circulating cytokines on overall survival and disease-free survival in cancer patients. Biomarkers Med 2014; 8 (02) 297-306
  • 33 Fujita N, Miyamoto T, Imai J. et al. CD24 is expressed specifically in the nucleus pulposus of intervertebral discs. Biochem Biophys Res Commun 2005; 338 (04) 1890-1896
  • 34 Aydemir E, Bayrak OF, Sahin F. et al. Characterization of cancer stem-like cells in chordoma. J Neurosurg 2012; 116 (04) 810-820
  • 35 Fatima F, Nawaz M. Stem cell-derived exosomes: roles in stromal remodeling, tumor progression, and cancer immunotherapy. Chin J Cancer 2015; 34 (12) 541-553
  • 36 Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res 2010; 316 (08) 1324-1331
  • 37 Dharmaraj N, Wang P, Carson DD. Cytokine and progesterone receptor interplay in the regulation of MUC1 gene expression. Mol Endocrinol 2010; 24 (12) 2253-2266
  • 38 Baudino TA, McKay C, Pendeville-Samain H. et al. c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev 2002; 16 (19) 2530-2543
  • 39 Nakai T, Mochida J, Sakai D. Synergistic role of c-Myc and ERK1/2 in the mitogenic response to TGF β-1 in cultured rat nucleus pulposus cells. Arthritis Res Ther 2008; 10 (06) R140
  • 40 Gulluoglu S, Sahin M, Tuysuz EC. et al. Leukemia inhibitory factor promotes aggressiveness of chordoma. Oncol Res 2017; 25 (07) 1177-1188
  • 41 Al Shihabi A, Davarifar A, Lam Nguyen HT. et al. (2021) Personalized chordoma organoids for drug discovery studies. bioRxiv 2021.05.27.446040