International Journal of Oral Biology

  • 제48권1호
  • /
  • Pages.1-7
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  • 2023
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  • 1226-7155(pISSN)
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  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
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Long-term exposure to gefitinib differentially regulates the endosomal sorting complex required for transport machinery, which accelerates the metastatic potential of oral squamous cell carcinoma cells

  • Mi Seong Kim (Department of Oral Physiology, Institute of Biomaterial-Implant, School of Dentistry, Wonkwang University) ;
  • Min Seuk Kim (Department of Oral Physiology, Institute of Biomaterial-Implant, School of Dentistry, Wonkwang University)
  • 투고 : 2023.02.08
  • 심사 : 2023.02.20
  • 발행 : 2023.03.31
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초록

Oral squamous cell carcinoma (OSCC), which accounts for approximately 90% of oral cancers, has a high rate of local recurrence and a poor prognosis despite improvements in treatment. Exosomes released from OSCC cells promote cell proliferation and metastasis. Although it is clear that the biogenesis of exosomes is mediated by the endosomal sorting complex required for transport (ESCRT) machinery, the gene expression pattern of ESCRT, depending on the cell type, remains elusive. The exosomal release from the human OSCC cell lines, HSC-3 and HSC-4, and their corresponding gefitinib-resistant sub-cell lines, HSC-3/GR and HSC-4/GR, was assessed by western blot and flow cytometry. The levels of ESCRT machinery proteins, including Hrs, Tsg101, and Alix, and whole-cell ubiquitination were evaluated by western blot. We observed that the basal level of exosomal release was higher in HSC-3/GR and HSC-4/GR cells than in HSC-3 and HSC-4 cells, respectively. Long-term gefitinib exposure of each cell line and its corresponding gefitinib-resistant sub-cell line differentially induced the expression of the ESCRT machinery. Furthermore, whole-cell ubiquitination and autophagic flux were shown to be increased in gefitinib-treated HSC-3 and HSC-4 cells. Our data indicate that the expression patterns of the ESCRT machinery genes are differentially regulated by the characteristics of cells, such as intracellular energy metabolism. Therefore, the expression patterns of the ESCRT machinery should be considered as a key factor to improve the treatment strategy for OSCC.

키워드

과제정보

We would like to thank prof. Sung Dae Cho in Seoul National University, who has kindly gifted us oral squamous cell carcinoma cell-line, HSC-3 and HSC-4.

참고문헌

  1. Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am 2015;24:491-508. doi: 10.1016/j.soc.2015.03.006
  2. Kurihara-Shimomura M, Sasahira T, Nakashima C, Kuniyasu H, Shimomura H, Kirita T. The multifarious functions of pyruvate kinase M2 in oral cancer cells. Int J Mol Sci 2018;19:2907. doi: 10.3390/ijms19102907
  3. Sasahira T, Kurihara M, Yamamoto K, Ueda N, Nakashima C, Matsushima S, Bhawal UK, Kirita T, Kuniyasu H. HuD promotes progression of oral squamous cell carcinoma. Pathobiology 2014;81:206-14. doi: 10.1159/000366022
  4. Vayrynen O, Astrom P, Nyberg P, Alahuhta I, Pirila E, Vilen ST, Aikio M, Heljasvaara R, Risteli M, Sutinen M, Salo T. Matrix metalloproteinase 9 inhibits the motility of highly aggressive HSC-3 oral squamous cell carcinoma cells. Exp Cell Res 2019;376:18-26. doi: 10.1016/j.yexcr.2019.01.018
  5. Hino M, Kamo M, Saito D, Kyakumoto S, Shibata T, Mizuki H, Ishisaki A. Transforming growth factor-β1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis. J Biochem 2016;159:631-40. doi: 10.1093/jb/mvw007
  6. Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 2019;9:19. doi:10.1186/s13578-019-0282-2
  7. Willms E, Johansson HJ, Mager I, Lee Y, Blomberg KE, Sadik M, Alaarg A, Smith CI, Lehtio J, El Andaloussi S, Wood MJ, Vader P. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep 2016;6:22519. doi: 10.1038/srep22519
  8. Larios J, Mercier V, Roux A, Gruenberg J. ALIX- and ESCRTIII-dependent sorting of tetraspanins to exosomes. J Cell Biol 2020;219:e201904113. doi: 10.1083/jcb.201904113
  9. Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S, Grivel JC. Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anticancer drug resistance. Mol Cancer 2019;18:55. doi: 10.1186/s12943-019-0965-7
  10. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer 2019;18:75. doi: 10.1186/s12943-019-0991-5
  11. Dong X, Bai X, Ni J, Zhang H, Duan W, Graham P, Li Y. Exosomes and breast cancer drug resistance. Cell Death Dis 2020;11:987. doi: 10.1038/s41419-020-03189-z
  12. Hu JL, Wang W, Lan XL, Zeng ZC, Liang YS, Yan YR, Song FY, Wang FF, Zhu XH, Liao WJ, Liao WT, Ding YQ, Liang L. CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelialmesenchymal transition in colorectal cancer. Mol Cancer 2019;18:91. doi: 10.1186/s12943-019-1019-x
  13. Wang X, Zhang H, Yang H, Bai M, Ning T, Deng T, Liu R, Fan Q, Zhu K, Li J, Zhan Y, Ying G, Ba Y. Exosome-delivered circRNA promotes glycolysis to induce chemoresistance through the miR-122-PKM2 axis in colorectal cancer. Mol Oncol 2020;14:539-55. doi: 10.1002/1878-0261.12629
  14. Zheng P, Chen L, Yuan X, Luo Q, Liu Y, Xie G, Ma Y, Shen L. Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. J Exp Clin Cancer Res 2017;36:53. doi: 10.1186/s13046-017-0528-y
  15. Ju Y, Bai H, Ren L, Zhang L. The role of exosome and the ESCRT pathway on enveloped virus infection. Int J Mol Sci 2021; 22:9060. doi: 10.3390/ijms22169060
  16. Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer 2019;1871:455-68. doi: 10.1016/j.bbcan.2019.04.004
  17. Tucker WC, Chapman ER. Role of synaptotagmin in Ca2+- triggered exocytosis. Biochem J 2002;366(Pt 1):1-13. doi: 10.1042/BJ20020776
  18. Gurung S, Perocheau D, Touramanidou L, Baruteau J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun Signal 2021;19:47. doi: 10.1186/s12964-021-00730-1
  19. Schmidt O, Teis D. The ESCRT machinery. Curr Biol 2012;22:R116-20. doi: 10.1016/j.cub.2012.01.028
  20. Peng H, Yang J, Li G, You Q, Han W, Li T, Gao D, Xie X, Lee BH, Du J, Hou J, Zhang T, Rao H, Huang Y, Li Q, Zeng R, Hui L, Wang H, Xia Q, Zhang X, He Y, Komatsu M, Dikic I, Finley D, Hu R. Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress. Cell Res 2017;27:657-74. doi: 10.1038/cr.2017.40
  21. Palacios-Ferrer JL, Garcia-Ortega MB, Gallardo-Gomez M, Garcia MA, Diaz C, Boulaiz H, Valdivia J, Jurado JM, AlmazanFernandez FM, Arias-Santiago S, Amezcua V, Peinado H, Vicente F, Perez Del Palacio J, Marchal JA. Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol Oncol 2021;15:407-28. doi: 10.1002/1878-0261.12823
  22. Jouida A, McCarthy C, Fabre A, Keane MP. Exosomes: a new perspective in EGFR-mutated lung cancer. Cancer Metastasis Rev 2021;40:589-601. doi: 10.1007/s10555-021-09962-6
  23. Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, Cvijic H, Ullmann AK, Stadler PF, Horn F. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 2007;110:1330-3. doi: 10.1182/blood-2007-03-081133
  24. Pessolano E, Belvedere R, Bizzarro V, Franco P, Marco I, Porta A, Tosco A, Parente L, Perretti M, Petrella A. Annexin A1 may induce pancreatic cancer progression as a key player of extracellular vesicles effects as evidenced in the in vitro MIA PaCa2 model system. Int J Mol Sci 2018;19:3878. doi: 10.3390/ijms19123878
  25. Zhu X, Shen H, Yin X, Yang M, Wei H, Chen Q, Feng F, Liu Y, Xu W, Li Y. Macrophages derived exosomes deliver miR223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res 2019;38:81. doi: 10.1186/s13046-019-1095-1
  26. Keklikoglou I, Cianciaruso C, Guc E, Squadrito ML, Spring LM, Tazzyman S, Lambein L, Poissonnier A, Ferraro GB, Baer C, Cassara A, Guichard A, Iruela-Arispe ML, Lewis CE, Coussens LM, Bardia A, Jain RK, Pollard JW, De Palma M. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat Cell Biol 2019;21(2):190-202. doi:10.1038/s41556-018-0256-3
  27. Han QF, Li WJ, Hu KS, Gao J, Zhai WL, Yang JH, Zhang SJ. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Mol Cancer 2022;21:207. doi: 10.1186/s12943-022-01671-0
  28. Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 2018;75:193-208. doi:10.1007/s00018-017-2595-9