International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Efficacy of biological inhibitors in three-dimensional culture models of oral squamous cell carcinoma

  • Eun Kyoung Kim (Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Sook Moon (Department of Dental Hygiene, Daejeon Health University) ;
  • Myung-Jin Lee (Department of Dental Hygiene, Division of Health Science, Baekseok University) ;
  • Dokyeong Kim (Precision Medicine Research Center, Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea)
  • Received : 2024.02.14
  • Accepted : 2024.03.08
  • Published : 2024.03.31
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Abstract

Despite advancements in therapeutic approaches, radiotherapy and cisplatin-based chemotherapy remain primary noninvasive treatments for patients with oral squamous cell carcinoma (OSCC). Moreover, the 5-year survival rate for patients with OSCC has remained almost unchanged for several decades, and many side effects of chemotherapy still exist. In this study, three-dimensional (3D) models of OSCC were established using fibroblasts, and the efficacy of various biological inhibitors was evaluated. A culture of epithelial cells with two types of fibroblasts (hTERT-hNOFs and cancer-associated fibroblasts) within a type I collagen matrix resulted in the formation of a continuous layer of tightly packed cells compared to models without fibroblasts. Furthermore, the effects of biological chemicals, including Y27632, latrunculin A, and verteporfin, on these models were investigated. The stratified formation of the epithelial layer and invasion in OSCC 3D-culture models were effectively inhibited by verteporfin, whereas invasion was weakly inhibited by Y27632 and latrunculin. Collectively, the developed OSCC 3D-culture models established with fibroblasts demonstrated the potential for drug screening, with verteporfin showing promising efficacy.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2021R1I1A1A01045571).

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49. doi: 10.3322/caac.21660
  2. Marcu L, van Doorn T, Olver I. Cisplatin and radiotherapy in the treatment of locally advanced head and neck cancer--a review of their cooperation. Acta Oncol 2003;42:315-25. doi: 10.1080/02841860310004364
  3. Kiyota N, Tahara M, Mizusawa J, Kodaira T, Fujii H, Yamazaki T, Mitani H, Iwae S, Fujimoto Y, Onozawa Y, Hanai N, Ogawa T, Hara H, Monden N, Shimura E, Minami S, Fujii T, Tanaka K, Homma A, Yoshimoto S, Oridate N, Omori K, Ueda T, Okami K, Ota I, Shiga K, Sugasawa M, Asakage T, Saito Y, Murono S, Nishimura Y, Nakamura K, Hayashi R; Head and Neck Cancer Study Group of the Japan Clinical Oncology Group (JCOGHNCSG). Weekly cisplatin plus radiation for postoperative head and neck cancer (JCOG1008): a multicenter, noninferiority, phase II/III randomized controlled trial. J Clin Oncol 2022;40:1980-90. doi: 10.1200/JCO.21.01293
  4. da Silva SD, Hier M, Mlynarek A, Kowalski LP, Alaoui-Jamali MA. Recurrent oral cancer: current and emerging therapeutic approaches. Front Pharmacol 2012;3:149. doi: 10.3389/fphar.2012.00149
  5. Badwelan M, Muaddi H, Ahmed A, Lee KT, Tran SD. Oral squamous cell carcinoma and concomitant primary tumors, what do we know? A review of the literature. Curr Oncol 2023;30:3721-34. doi: 10.3390/curroncol30040283
  6. Jerjes W, Upile T, Petrie A, Riskalla A, Hamdoon Z, Vourvachis M, Karavidas K, Jay A, Sandison A, Thomas GJ, Kalavrezos N, Hopper C. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol 2010;2:9. doi: 10.1186/1758-3284-2-9
  7. Kapalczynska M, Kolenda T, Przybyla W, Zajaczkowska M, Teresiak A, Filas V, Ibbs M, Blizniak R, Luczewski L, Lamperska K. 2D and 3D cell cultures - a comparison of different types of cancer cell cultures. Arch Med Sci 2018;14:910-9. doi: 10.5114/aoms.2016.63743
  8. Van Norman GA. Limitations of animal studies for predicting toxicity in clinical trials: is it time to rethink our current approach? JACC Basic Transl Sci 2019;4:845-54. doi: 10.1016/j.jacbts.2019.10.008
  9. Almagro J, Messal HA, Elosegui-Artola A, van Rheenen J, Behrens A. Tissue architecture in tumor initiation and progression. Trends Cancer 2022;8:494-505. doi: 10.1016/j.trecan.2022.02.007
  10. Chitturi Suryaprakash RT, Shearston K, Farah CS, Fox SA, Iqbal MM, Kadolsky U, Zhong X, Saxena A, Kujan O. A novel preclinical in vitro 3D model of oral carcinogenesis for biomarker discovery and drug testing. Int J Mol Sci 2023;24:4096. doi: 10.3390/ijms24044096
  11. Kwon JS, Illeperuma RP, Kim J, Kim KM, Kim KN. Cytotoxicity evaluation of zinc oxide-eugenol and non-eugenol cements using different fibroblast cell lines. Acta Odontol Scand 2014;72:64-70. doi: 10.3109/00016357.2013.798871
  12. Illeperuma RP, Kim DK, Park YJ, Son HK, Kim JY, Kim J, Lee DY, Kim KY, Jung DW, Tilakaratne WM, Kim J. Areca nut exposure increases secretion of tumor-promoting cytokines in gingival fibroblasts that trigger DNA damage in oral keratinocytes. Int J Cancer 2015;137:2545-57. doi: 10.1002/ijc.29636
  13. Kim EK, Moon S, Kim DK, Zhang X, Kim J. CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in oral squamous cell carcinoma. PLoS One 2018;13:e0188847. doi: 10.1371/journal.pone.0188847
  14. Kim DK, Kim EK, Jung DW, Kim J. Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. PLoS One 2019;14:e0214553. doi: 10.1371/journal.pone.0214553
  15. Lee EJ, Kim J, Lee SA, Kim EJ, Chun YC, Ryu MH, Yook JI. Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells. Exp Mol Med 2005;37:379-90. doi:10.1038/emm.2005.48
  16. Kitamura N, Sento S, Yoshizawa Y, Sasabe E, Kudo Y, Yamamoto T. Current trends and future prospects of molecular targeted therapy in head and neck squamous cell carcinoma. Int J Mol Sci 2020;22:240. doi: 10.3390/ijms22010240
  17. Miserocchi G, Cocchi C, De Vita A, Liverani C, Spadazzi C, Calpona S, Di Menna G, Bassi M, Meccariello G, De Luca G, Campobassi A, Maddalena Tumedei M, Bongiovanni A, Fausti V, Cotelli F, Ibrahim T, Mercatali L. Three-dimensional collagen-based scaffold model to study the microenvironment and drug-resistance mechanisms of oropharyngeal squamous cell carcinomas. Cancer Biol Med 2021;18:502-16. doi: 10.20892/j.issn.2095-3941.2020.0482
  18. Chitturi Suryaprakash RT, Kujan O, Shearston K, Farah CS. Three-dimensional cell culture models to investigate oral carcinogenesis: a scoping review. Int J Mol Sci 2020;21:9520. doi: 10.3390/ijms21249520
  19. Wensink GE, Elias SG, Mullenders J, Koopman M, Boj SF, Kranenburg OW, Roodhart JML. Patient-derived organoids as a predictive biomarker for treatment response in cancer patients. NPJ Precis Oncol 2021;5:30. doi: 10.1038/s41698-021-00168-1
  20. Kang MJ, Jung KW, Bang SH, Choi SH, Park EH, Yun EH, Kim HJ, Kong HJ, Im JS, Seo HG; Community of Population- Based Regional Cancer Registries*. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2020. Cancer Res Treat 2023;55:385-99. doi: 10.4143/crt.2023.447
  21. Wen J, Ma L, Zu T, Wang N, Zhang T, Liang J, Sun Y, Zhang Y, Liu R, Zhang S, Wu Y. ROCK inhibitor inhibits the growth and migration of oral squamous cell carcinoma via up-regulated autophagy by suppressing AKT/mTOR pathway. Research Square [Preprint]. 2023 [cited 2024 Feb 14]. Available from: https://doi.org/10.21203/rs.3.rs-2376978/v1
  22. Konishi H, Kikuchi S, Ochiai T, Ikoma H, Kubota T, Ichikawa D, Fujiwara H, Okamoto K, Sakakura C, Sonoyama T, Kokuba Y, Sasaki H, Matsui T, Otsuji E. Latrunculin a has a strong anticancer effect in a peritoneal dissemination model of human gastric cancer in mice. Anticancer Res 2009;29:2091-7.
  23. Feng J, Gou J, Jia J, Yi T, Cui T, Li Z. Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer. Onco Targets Ther 2016;9:5371-81. doi: 10.2147/OTT.S109979
  24. Wei H, Wang F, Wang Y, Li T, Xiu P, Zhong J, Sun X, Li J. Verteporfin suppresses cell survival, angiogenesis and vasculogenic mimicry of pancreatic ductal adenocarcinoma via disrupting the YAP-TEAD complex. Cancer Sci 2017;108:478-87. doi: 10.1111/cas.13138
  25. Liao T, Wei WJ, Wen D, Hu JQ, Wang Y, Ma B, Cao YM, Xiang J, Guan Q, Chen JY, Sun GH, Zhu YX, Li DS, Ji QH. Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway. J Cancer 2018;9:1329-36. doi: 10.7150/jca.21915
  26. Wei C, Li X. Verteporfin inhibits cell proliferation and induces apoptosis in different subtypes of breast cancer cell lines without light activation. BMC Cancer 2020;20:1042. doi: 10.1186/s12885-020-07555-0
  27. Liu K, Du S, Gao P, Zheng J. Verteporfin suppresses the proliferation, epithelial-mesenchymal transition and stemness of head and neck squamous carcinoma cells via inhibiting YAP1. J Cancer 2019;10:4196-207. doi: 10.7150/jca.34145
  28. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006;6:392-401. doi: 10.1038/nrc1877