The mouse oral carcinoma (MOC) model: A 10-year retrospective on model development and head and neck cancer investigations

Kono, Michihisa; Saito, Shin; Egloff, Ann Marie; Allen, Clint; Uppaluri, Ravindra

doi:10.1016/j.oraloncology.2022.106012

Cited by 19 publications

(11 citation statements)

References 117 publications

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“…Nevertheless, the developed MOC1-HPV K1 tumor model still presents with increased radiosensitivity similar to that observed in patients. To our knowledge, all available murine OSCC cell lines are derived from carcinogen-induced tumors, therefore we have chosen MOC1 for parental cell line since it has been extensively used in various studies of OSCC biology (reviewed in [ 87 ]). Another limitation of the study is that the transcriptomic analysis was performed only on the monoclonal cell lines in vitro.…”

Section: Discussionmentioning

confidence: 99%

HPV-positive murine oral squamous cell carcinoma: development and characterization of a new mouse tumor model for immunological studies

Modic¹,

Čemažar²,

Markelc³

et al. 2023

J Transl Med

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Background Infection with high-risk human papillomavirus (HPV) strains is one of the risk factors for the development of oral squamous cell carcinoma (OSCC). Some patients with HPV-positive OSCC have a better prognosis and respond better to various treatment modalities, including radiotherapy or immunotherapy. However, since HPV can only infect human cells, there are only a few immunocompetent mouse models available that enable immunological studies. Therefore, the aim of our study was to develop a transplantable immunocompetent mouse model of HPV-positive OSCC and characterize it in vitro and in vivo. Methods Two monoclonal HPV-positive OSCC mouse cell lines were established by inducing the expression of HPV-16 oncogenes E6 and E7 in the MOC1 OSCC cell line using retroviral transduction. After confirming stable expression of HPV-16 E6 and E7 with quantitative real-time PCR and immunofluorescence staining, the cell lines were further characterized in vitro using proliferation assay, wound healing assay, clonogenic assay and RNA sequencing. In addition, tumor models were characterized in vivo in C57Bl/6NCrl mice in terms of their histological properties, tumor growth kinetics, and radiosensitivity. Furthermore, immunofluorescence staining of blood vessels, hypoxic areas, proliferating cells and immune cells was performed to characterize the tumor microenvironment of all three tumor models. Results Characterization of the resulting MOC1-HPV cell lines and tumor models confirmed stable expression of HPV-16 oncogenes and differences in cell morphology, in vitro migration capacity, and tumor microenvironment characteristics. Although the cell lines did not differ in their intrinsic radiosensitivity, one of the HPV-positive tumor models, MOC1-HPV K1, showed a significantly longer growth delay after irradiation with a single dose of 15 Gy compared to parental MOC1 tumors. Consistent with this, MOC1-HPV K1 tumors had a lower percentage of hypoxic tumor area and a higher percentage of proliferating cells. Characteristics of the newly developed HPV-positive OSCC tumor models correlate with the transcriptomic profile of MOC1-HPV cell lines. Conclusions In conclusion, we developed and characterized a novel immunocompetent mouse model of HPV-positive OSCC that exhibits increased radiosensitivity and enables studies of immune-based treatment approaches in HPV-positive OSCC.

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Section: Discussionmentioning

confidence: 99%

HPV-positive murine oral squamous cell carcinoma: development and characterization of a new mouse tumor model for immunological studies

Modic¹,

Čemažar²,

Markelc³

et al. 2023

J Transl Med

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“…DMBA, a potent organ-specific carcinogen, not only acts as an immunosuppressor but also serves as a tumor initiator, making it widely used in cancer research. Tumor progression can be induced by DMBA alone or in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA) (Kono et al 2022). In a study by Judd et al, mice were treated with DMBA administered orally twice weekly.…”

Section: Dmba Modelmentioning

confidence: 99%

Mouse Models for Head and Neck Squamous Cell Carcinoma

Zhou,

Liu,

Amornphimoltham

et al. 2024

J Dent Res

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The prognosis and survival rate of head and neck squamous cell carcinoma (HNSCC) have remained unchanged for years, and the pathogenesis of HNSCC is still not fully understood, necessitating further research. An ideal animal model that accurately replicates the complex microenvironment of HNSCC is urgently needed. Among all the animal models for preclinical cancer research, tumor-bearing mouse models are the best known and widely used due to their high similarity to humans. Currently, mouse models for HNSCC can be broadly categorized into chemical-induced models, genetically engineered mouse models (GEMMs), and transplanted mouse models, each with its distinct advantages and limitations. In chemical-induced models, the carcinogen spontaneously initiates tumor formation through a multistep process. The resemblance of this model to human carcinogenesis renders it an ideal preclinical platform for studying HNSCC initiation and progression from precancerous lesions. The major drawback is that these models are time-consuming and, like human cancer, unpredictable in terms of timing, location, and number of lesions. GEMMs involve transgenic and knockout mice with gene modifications, leading to malignant transformation within a tumor microenvironment that recapitulates tumorigenesis in vivo, including their interaction with the immune system. However, most HNSCC GEMMs exhibit low tumor incidence and limited prognostic significance when translated to clinical studies. Transplanted mouse models are the most widely used in cancer research due to their consistency, availability, and efficiency. Based on the donor and recipient species matching, transplanted mouse models can be divided into xenografts and syngeneic models. In the latter, transplanted cells and host are from the same strain, making syngeneic models relevant to study functional immune system. In this review, we provide a comprehensive summary of the characteristics, establishment methods, and potential applications of these different HNSCC mouse models, aiming to assist researchers in choosing suitable animal models for their research.

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“…These cell lines were established from 7, 12-dimethylbenz(a) anthracene (DMBA)-induced oral squamous cell tumors in mice and have been used in numerous preclinical studies of oral cancer. 1 In recent years, concerns have arisen about using head and neck cancer cell lines in the subcutaneous flank, which may not represent the immune microenvironment of the upper aerodigestive tract. Not surprisingly, in recent years multiple laboratory groups have transitioned to using orthotopic models, injecting murine cell lines into the buccal mucosa, tongue, or other sites.…”

Section: Introductionmentioning

confidence: 99%

“…Among these, the mouse oral cancer (MOC) cell lines are among the most popular and well established. These cell lines were established from 7, 12‐dimethylbenz(a) anthracene (DMBA)‐induced oral squamous cell tumors in mice and have been used in numerous preclinical studies of oral cancer 1 …”

Section: Introductionmentioning

confidence: 99%

Characterization of the tumor microenvironment in the mouse oral cancer (MOC1) model after orthotopic implantation in the buccal mucosa

Kansal,

Kinney,

Schmitt

2024

Head & Neck

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BackgroundPreclinical models are invaluable for studies of head and neck cancer. There is growing interest in the use of orthotopic syngeneic models, wherein cell lines are injected into the oral cavity of immunocompetent mice. In this brief report, we describe injection of mouse oral cancer 1 (MOC1) cells into the buccal mucosa and illustrate the tumor growth pattern, lymph node response, and changes in the tumor immune microenvironment over time.MethodsMOC1 cells were injected into the buccal mucosa of C57BL6 mice. Animals were sacrificed at 7, 14, 21, or 27 days. Tumors and lymph nodes were analyzed by flow cytometry.ResultsAll mice developed tumors by day 7 and required euthanasia for tumor burden and/or weight loss by day 27. Lymph node mapping showed that these tumors reliably drain to a submandibular lymph node. The proportion of intratumoral CD8+ T cells decreased over time, while neutrophilic myeloid cells increased dramatically. Growth of orthotopic MOC2 and MOC22 also showed similar growth patterns versus published data in flank tumors.ConclusionsWhen used orthotopically in the buccal mucosa, the MOC1 model induces a robust lymph node response and distinct pattern of immune cell infiltration, with peak immune infiltration by day 14.

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The mouse oral carcinoma (MOC) model: A 10-year retrospective on model development and head and neck cancer investigations

Cited by 19 publications

References 117 publications

HPV-positive murine oral squamous cell carcinoma: development and characterization of a new mouse tumor model for immunological studies

HPV-positive murine oral squamous cell carcinoma: development and characterization of a new mouse tumor model for immunological studies

Mouse Models for Head and Neck Squamous Cell Carcinoma

Characterization of the tumor microenvironment in the mouse oral cancer (MOC1) model after orthotopic implantation in the buccal mucosa

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