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Selecting the Appropriate Oral Cancer Cell Line: Characteristic-Based Recommendations from a Systematic Review

Authors

  • Jamison Wijaya

    Faculty of Dentistry, Universitas Trisakti, Jakarta, Indonesia

  • Indrayadi Gunardi

    Oral Medicine Department, Universitas Trisakti, Jakarta, Indonesia.

  • Julvyn Julvyn

    Faculty of Dentistry, Universitas Trisakti, Jakarta, Indonesia

  • Christopher Lim

    Faculty of Dentistry, Universitas Trisakti, Jakarta, Indonesia

  • Benny Nicolas Johannis

    Faculty of Dentistry, Universitas Trisakti, Jakarta, Indonesia

  • Firstine Kelsi Hartanto

    Oral Medicine Department, Universitas Trisakti, Jakarta, Indonesia

  • Adrianus Rajasa

    Oral Medicine Department, Universitas Trisakti, Jakarta, Indonesia

  • Rahmi Amtha

    Oral Medicine Department, Universitas Trisakti, Jakarta, Indonesia.

  • Elizabeth Fitriana Sari

    Dentistry and Oral Health Department, La Trobe University, Rural Health School, Australia

DOI:

https://doi.org/10.30683/1929-2279.2025.14.28

Keywords:

Cell line, human, in vitro, oral squamous cell carcinoma, oral cancer, systematic review

Abstract

Introduction: Oral squamous cell carcinoma (OSCC) research often relies on in vitro models to study tumor behaviour and evaluate therapeutic agents. However, variability in cell line characteristics and limited guidance on their selection pose challenges to research consistency and translational accuracy.

Objective: To provide a comprehensive evaluation of OSCC cell lines based on anatomical origin/site, biological features and associated risk factors, offering evidence-based recommendations for their appropriate use.

Method: A systematic review was conducted in PubMed database covering the period 1972 to 2024 using the keywords “human,” “oral squamous cell carcinoma,” and “cell line.” Inclusion criteria were English full-text publications describing human-derived OSCC cell lines. Cell lines of animal origin or with known contamination were excluded from this study.

Results: Out of 524 records, 106 publications were analyzed. Japan and the USA led in cell line development. Most cell lines originated from male patients and the tongue was the predominant anatomical site for OSCC. Highly cited lines such as HSC-3, CAL-27, and SAS were favored for studies on metastasis, immune markers, and drug testing. Cell lines were categorized based on single or multiple risk exposures, including tobacco, alcohol, betel quid, and HPV infection.

Conclusion: This review provides an evidence-based framework for selecting OSCC cell lines by anatomical origin/site, molecular features, and documented etiologic exposures. Therefore, researchers should align cell-line selection with the relevant characteristic background and the specific experimental goal (e.g., metastasis, immune-marker, or drug testing), prioritizing well-characterized models when reproducibility and translational relevance are key.

References

[1] Fatima J, Fatima E, Mehmood F, Ishtiaq I, Khan MA, Khurshid HMS, et al. Comprehensive Analysis of Oral Squamous Cell Carcinomas: Clinical, Epidemiological, and Histopathological Insights With a Focus on Prognostic Factors and Survival Time. Cureus 2024; 16(2): e54394.

[2] Geum DH, Roh YC, Yoon SY, Kim HG, Lee JH, Song JM, et al. The impact factors on 5-year survival rate in patients operated with oral cancer. J Korean Assoc Oral Maxillofac Surg 2013; 39(5): 207.

[3] Mauceri R, Bazzano M, Coppini M, Tozzo P, Panzarella V, Campisi G. Diagnostic delay of oral squamous cell carcinoma and the fear of diagnosis: A scoping review. Front Psychol 2022; 13.

[4] Kim H, Lee SM, Ahn KM. The epidemiological and histopathological factors for delayed local recurrence in oral squamous cell carcinoma. Maxillofac Plast Reconstr Surg 2024; 46(1): 38.

[5] Bugshan A, Farooq I. Oral squamous cell carcinoma: metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis. F1000Res 2020; 9: 229.

[6] Gunardi I, Sufiawati I, Goenawan H, Herawati DMD, Lesmana R, Abdullah AG. Research Trends in Molecular Biological Studies on Oral Squamous Cell Carcinoma: A Bibliometric Analysis. Oncol Rev 2023; 17: 11585.

[7] Sharma MP, Shukla S, Misra G. Recent advances in breast cancer cell line research. Int J Cancer 2024; 154(10): 1683-93.

[8] Kurniawan A, Amtha R, Gunardi I, Heriandi A, Sari E. The Impact of Electronic and Conventional Cigarette Use towards Saliva Profile and Oral Microbiota in Adolescents. Asian Pacific Journal of Cancer Prevention 2025; 26(1): 309-18.

[9] Acharya SK, Shai S, Choon YF, Gunardi I, Hartanto FK, Kadir K, et al. Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges. Biomedicines 2024; 12(9).

[10] Amtha R, Gunardi I, Widyarman AS, Herwanto T, Hartanto FK, Vincent-Chong VK. Salivary Profile Analysis Based on Oral Cancer Risk Habits: An Observational Cross-Sectional Study. Biomedicines 2024; 12(8): 1748.

[11] Hartanto FK. Cd8+ expression in oral potentially malignant disorders associated with risk factors in selected population of east Indonesia. Odonto : Dental Journal 2023; 10(1): 52.

[12] Jasim A, Li X, Octavia A, Gunardi I, Crocombe L, Sari EF. The association between betel quid use and oral potentially malignant and malignant disorders in Southeast Asian and Pacific regions: a systematic review and meta-analysis with GRADE evidence profile. Frontiers in Oral Health 2024; 5.

[13] Momose F, Araida T, Negishi A, Ichijo H, Shioda S, Sasaki S. Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. Journal of Oral Pathology & Medicine 1989; 18(7): 391-5.

[14] Almahmoudi R, Salem A, Hadler‐Olsen E, Svineng G, Salo T, Al‐Samadi A. The effect of interleukin‐17F on vasculogenic mimicry in oral tongue squamous cell carcinoma. Cancer Sci 2021; 112(6): 2223-32.

[15] Kudo Y, Kitajjma S, Sato S, Miyauchi M, Ogawa I, Takata T. Establishment of an oral squamous cell carcinoma cell line with high invasive and p27 degradation activities from a lymph node metastasis. Oral Oncol 2003; 39(5): 515-20.

[16] Tanaka H, Toyoshima T, Sonoda K, Kitamura R, Sasaguri M, Kawano S, et al. Apoptotic function of tumor-associated antigen RCAS1 in oral squamous cell carcinoma. J Transl Med 2014; 12(1): 112.

[17] Velmurugan BK, Hua CH, Tsai MH, Lee CP, Chung CM, Ko YC. Combination of celecoxib and calyculin-A inhibits epithelial-mesenchymal transition in human oral cancer cells. Biotechnic & Histochemistry 2020; 95(5): 341-8.

[18] Baba O, Hasegawa S, Nagai H, Uchida F, Yamatoji M, Kanno NI, et al. MicroRNA‐155‐5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. Journal of Oral Pathology & Medicine 2016; 45(4): 248-55.

[19] Sakakura K, Takahashi H, Kaira K, Toyoda M, Murata T, Ohnishi H, et al. Relationship between tumor-associated macrophage subsets and CD47 expression in squamous cell carcinoma of the head and neck in the tumor microenvironment. Laboratory Investigation 2016; 96(9): 994-1003.

[20] Gioanni J, Fischel JL, Lambert JC, Demard F, Mazeau C, Zanghellini E, et al. Two new human tumor cell lines derived from squamous cell carcinomas of the tongue: establishment, characterization and response to cytotoxic treatment. Eur J Cancer Clin Oncol 1988; 24(9): 1445-55.

[21] Azzi L, Celesti F, Chiaravalli AM, Shaik AKB, Shallak M, Gatta A, et al. Novel vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma. Front Immunol 2024; 15.

[22] Ye XJ, Yang JG, Tan YQ, Chen XJ, Zhou G. Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma. Anticancer Agents Med Chem 2021; 21(6): 766-74.

[23] Yu L, Shao X, Huo L, Zhang T. Long Non-Coding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes Cell Proliferation and Migration by Regulating miR-143-3p and MAGE Family Member A9 (MAGEA9) in Oral Squamous Cell Carcinoma. Medical Science Monitor 2020; 26.

[24] Katz J, Jakymiw A, Ducksworth MK, Stewart CM, Bhattacharyya I, Cha S, et al. CIP2A expression and localization in oral carcinoma and dysplasia. Cancer Biol Ther 2010; 10(7): 694-9.

[25] Wang XM, Jiang Y. [Effect of disulfiram on epithelial-mesenchymal transformation of oral squamous cell carcinoma cells]. Shanghai Kou Qiang Yi Xue 2020; 29(2): 138-45.

[26] Takahashi K, Kanazawa H, Akiyama Y, Tazaki S, Takahara M, Muto T, et al. Establishment and characterization of a cell line (SAS) from poorly differentiated human squamous cell carcinoma of the tongue. Journal of the Japanese Stomatological Society 1989; 1: 20-8.

[27] Ito Y, Suzuki T, Shimomura M, Takenouchi K, Ohnuki K, Shoda K, et al. Feasibility of Intratumoral Administration With EPHB4‐CAR‐T Cells for the Treatment of Oral Squamous Cell Carcinoma. Cancer Sci 2025; 116(5): 1227-38.

[28] Chu YH, Su CW, Hsieh YS, Chen PN, Lin CW, Yang SF. Carbonic Anhydrase III Promotes Cell Migration and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. Cells 2020; 9(3): 704.

[29] Todoroki K, Ogasawara S, Akiba J, Nakayama M, Naito Y, Seki N, et al. CD44v3+/CD24− cells possess cancer stem cell-like properties in human oral squamous cell carcinoma. Int J Oncol 2016; 48(1): 99-109.

[30] Pai S, Bamodu OA, Lin YK, Lin CS, Chu PY, Chien MH, et al. CD47-SIRPα Signaling Induces Epithelial-Mesenchymal Transition and Cancer Stemness and Links to a Poor Prognosis in Patients with Oral Squamous Cell Carcinoma. Cells 2019; 8(12): 1658.

[31] Sasabe E, Tomomura A, Yamamoto T. The involvement of epidermal growth factor receptor/protein kinase B signaling in the tumor intrinsic PD‐L1‐induced malignant potential of oral squamous cell carcinoma. Journal of Oral Pathology & Medicine 2024; 53(5): 310-20.

[32] Rheinwald JG, Beckett MA. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res 1981; 41(5): 1657-63.

[33] Wang S, Li F, Fan H, Xu J, Hu Z. Expression of PIWIL2 in oral cancer and leukoplakia: Prognostic implications and insights from tumors. Cancer Biomarkers 2019; 26(1): 11-20.

[34] Stenberg J, Spiegelberg D, Karlsson H, Nestor M. Choice of labeling and cell line influences interactions between the Fab fragment AbD15179 and its target antigen CD44v6. Nucl Med Biol 2014; 41(2): 140-7.

[35] Hebert C, Norris K, Della Coletta R, Reynolds M, Ordóñez J, Sauk JJ. Cell surface colligin/Hsp47 associates with tetraspanin protein CD9 in epidermoid carcinoma cell lines. J Cell Biochem 1999; 73(2): 248-58.

[36] Kudo Y, Ogawa I, Kitagawa M, Kitajima S, Samadarani Siriwardena BSM, Aobara N, et al. Establishment and characterization of a spindle cell squamous carcinoma cell line. Journal of Oral Pathology & Medicine 2006; 35(8): 479-83.

[37] Yaginuma T, Gao J, Nagata K, Muroya R, Fei H, Nagano H, et al. p130Cas induces bone invasion by oral squamous cell carcinoma by regulating tumor epithelial-mesenchymal transition and cell proliferation. Carcinogenesis 2020; 41(8): 1038-48.

[38] Kaneko M, Ohishi T, Takei J, Sano M, Nakamura T, Hosono H, et al. Anti-EpCAM monoclonal antibody exerts antitumor activity against oral squamous cell carcinomas. Oncol Rep 2020; 44(6): 2517-26.

[39] Sato S, Miyauchi M, Kato M, Kitajima S, Kitagawa S, Hiraoka M, et al. Upregulated CD44v9 Expression Inhibits the Invasion of Oral Squamous Cell Carcinoma Cells. Pathobiology 2004; 71(4): 171-5.

[40] Zang W, Liu J, Geng F, Liu D, Zhang S, Li Y, et al. Butyrate promotes oral squamous cell carcinoma cells migration, invasion and epithelial-mesenchymal transition. Peer J 2022; 10: e12991.

[41] Zheng M, Huang Y, Fei W, Shen Y, Nie X, Gao MY. [Expression of Tyrosine Kinase Receptor 2 in Oral Squamous Cell Carcinoma and the Effect on Cell Proliferation and Migration and Epithelial-Mesenchymal Transition Process]. Sichuan Da Xue Xue Bao Yi Xue Ban 2023; 54(2): 342-9.

[42] Wang SJ, Earle C, Wong G, Bourguignon LYW. Role of hyaluronan synthase 2 to promote CD44‐dependent oral cavity squamous cell carcinoma progression. Head Neck 2013; 35(4): 511-20.

[43] Park S, Jang WJ, Jeong CH. Nano-biomechanical Validation of Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinomas. Biol Pharm Bull 2016; 39(9): 1488-95.

[44] Wang M, Qiu Y, Zhang R, Gao L, Wang X, Bi L, et al. MEHP promotes the proliferation of oral cancer cells via down regulation of miR-27b-5p and miR-372-5p. Toxicology in vitro 2019; 58: 35-41.

[45] Hebert C, Norris K, Sauk JJ. Targeting of Human Squamous Carcinomas by SPA470-doxorubicin Immunoconjugates. J Drug Target 2003; 11(2): 101-7.

[46] Yoshiya M. A fibronectin-producing cell line established from a human squamous cell carcinoma of the tongue and its characterization. Japanese Journal of Oral & Maxillofacial Surgery 1990; 36(4): 868-80.

[47] Yasukochi A, Kawakubo-Yasukochi T, Morioka M, Hazekawa M, Nishinakagawa T, Ono K, et al. Regulation of collagen type XVII expression by miR203a-3p in oral squamous cell carcinoma cells. The Journal of Biochemistry 2019; 166(2): 163-73.

[48] Wu Y, Zhang G, Yin P, Wen J, Su Y, Zhang X. Brusatol improves the efficacy of an anti-mouse-PD-1 antibody via inhibiting programmed cell death 1 ligand 1 expression in a murine head and neck squamous cell carcinoma model. Arch Oral Biol 2024; 166: 106043.

[49] Chien M, Lee T, Kao C, Yang S, Lee W. Terbinafine inhibits oral squamous cell carcinoma growth through anti‐cancer cell proliferation and anti‐angiogenesis. Mol Carcinog 2012; 51(5): 389-99.

[50] Li Y, Xiang ZY, Xiong J, Hou ZW, Zhu Z, Bao WW. RN181 regulates the biological behaviors of oral squamous cell carcinoma cells via mediating ERK/MAPK signaling pathway. Acta Histochem 2021; 123(5): 151733.

[51] Schminke B, Shomroni O, Salinas G, Bremmer F, Kauffmann P, Schliephake H, et al. Prognostic factor identification by screening changes in differentially expressed genes in oral squamous cell carcinoma. Oral Dis 2023; 29(1): 116-27.

[52] Ye D, Zhou X, Pan H, Jiang Q, Zhong L, Chen W, et al. Establishment and characterization of an HPV16 E6/E7-expressing oral squamous cell carcinoma cell line with enhanced tumorigenicity. Medical Oncology 2011; 28(4): 1331-7.

[53] Paolini R, Moore C, Matthyssen T, Cirillo N, McCullough M, Farah CS, et al. Transcriptional regulation of glucose transporters in human oral squamous cell carcinoma cells. Journal of Oral Pathology & Medicine 2022; 51(8): 679-83.

[54] Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S. Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 2007; 28(1): 81-92.

[55] Ji ZW, Oku N, Umeda M, Komori T. Establishment of an oral squamous cell carcinoma cell line(NOS-1) exhibiting amplification of the erbB-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantationof the cell line. Oral Oncol 2001; 37(4): 386-92.

[56] White JS, Weissfeld JL, Ragin CCR, Rossie KM, Martin CL, Shuster M, et al. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol 2007; 43(7): 701-12.

[57] Hamid S, Lim KP, Zain RB, Ismail SM, Lau SH, Mustafa WMW, et al. Establishment and characterization of Asian oral cancer cell lines as in vitro models to study a disease prevalent in Asia. Int J Mol Med 2007; 19(3): 453-60.

[58] Lin S, Liu C, Chiu C, Chang S, Lu S, Chen Y. Establishment of OC3 oral carcinoma cell line and identification of NF‐κB activation responses to areca nut extract. Journal of Oral Pathology & Medicine 2004; 33(2): 79-86.

[59] Wong DYK, Chang KW, Chen CF, Chang RCS. Characterization of two new cell lines derived from oral cavity human squamous cell carcinomas—OC1 and OC2. Journal of Oral and Maxillofacial Surgery 1990; 48(4): 385-90.

[60] Steenbergen RD, Hermsen MA, Walboomers JM, Joenje H, Arwert F, Meijer CJ, et al. Integrated human papillomavirus type 16 and loss of heterozygosity at 11q22 and 18q21 in an oral carcinoma and its derivative cell line. Cancer Res 1995; 55(22): 5465-71.

[61] Boyd MR. The NCI In vitro Anticancer Drug Discovery Screen. In: Anticancer Drug Development Guide. Totowa, NJ: Humana Press 1997; pp. 23-42.

[62] Gillet JP, Varma S, Gottesman MM. The Clinical Relevance of Cancer Cell Lines. JNCI Journal of the National Cancer Institute 2013; 105(7): 452-8.

[63] Ichimura N, Urata Y, Kobayashi T, Ebata R, Matsumoto H, Hibi H. Mutational landscape of Japanese patients with oral squamous cell carcinoma from comprehensive genomic profiling tests. Oral Oncol 2024; 159: 107079.

[64] de Camargo Cancela M, Voti L, Guerra-Yi M, Chapuis F, Mazuir M, Curado MP. Oral cavity cancer in developed and in developing countries: population-based incidence. Head Neck 2010; 32(3): 357-67.

[65] Mahboubi K, Nakoneshny SC, Sauro K, Roberts S, Hart R, Matthews TW, et al. The Association of Ethnicity and Oncologic Outcomes for Oral Cavity Squamous Cell Carcinoma (OSCC). Cancers (Basel) 2024; 16(11): 2117.

[66] Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009; 45(4-5): 309-16.

[67] Chen PH, Mahmood Q, Mariottini GL, Chiang TA, Lee KW. Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers. Biomed Res Int 2017; 2017: 1-25.

[68] Lee YC, Young CK, Chien HT, Chin SC, Iandelli A, Liao CT, et al. Characteristics and outcome differences in male and female oral cavity cancer patients in Taiwan. Medicine 2021; 100(44): e27674.

[69] Angadi PV, Patil PV, Angadi V, Mane D, Shekar S, Hallikerimath S, et al. Immunoexpression of Epithelial Mesenchymal Transition Proteins E-Cadherin, β-Catenin, and N-Cadherin in Oral Squamous Cell Carcinoma. Int J Surg Pathol 2016; 24(8): 696-703.

[70] Huang Z, Su Q, Li W, Ren H, Huang H, Wang A. MCTS1 promotes invasion and metastasis of oral cancer by modifying the EMT process. Ann Transl Med 2021; 9(12): 997-997.

[71] Kim SK, Cho SW. The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment. Front Pharmacol 2022; 13.

[72] Dine J, Gordon R, Shames Y, Kasler MK, Barton-Burke M. Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer. Asia Pac J Oncol Nurs 2017; 4(2): 127-35.

[73] Kythreotou A, Siddique A, Mauri FA, Bower M, Pinato DJ. PD-L1. J Clin Pathol 2018; 71(3): 189-94.

[74] Zhou X, Cao Y, Zhou M, Han M, Liu M, Hu Y, et al. Decreased CD44v3 expression impairs endometrial stromal cell proliferation and decidualization in women with recurrent implantation failure. Reproductive Biology and Endocrinology 2022; 20(1): 170.

[75] Vychaktami KK, Amtha R, Gunardi I, Zain RB. The effect of herbal medicine in reducing the severity of oral lichen planus: A systematic review and meta-analysis. Dental Journal (Majalah Kedokteran Gigi) 2022; 55(3): 165-173.

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2025-12-31

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Vol. 14 (2025)

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Selecting the Appropriate Oral Cancer Cell Line: Characteristic-Based Recommendations from a Systematic Review. (2025). Journal of Cancer Research Updates, 14, 279-289. https://doi.org/10.30683/1929-2279.2025.14.28

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