Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, Zhejiang, China.
Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
J Dent Res. 2024 Jun;103(6):585-595. doi: 10.1177/00220345241240997. Epub 2024 May 9.
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.
头颈部鳞状细胞癌 (HNSCC) 的预后和生存率多年来一直没有改变,其发病机制仍不完全清楚,需要进一步研究。迫切需要一种能够准确复制 HNSCC 复杂微环境的理想动物模型。在所有用于临床前癌症研究的动物模型中,肿瘤荷瘤小鼠模型由于与人类高度相似而最为知名和广泛应用。目前,HNSCC 的小鼠模型可大致分为化学诱导模型、基因工程小鼠模型 (GEMM) 和移植小鼠模型,每种模型都有其独特的优势和局限性。在化学诱导模型中,致癌物通过多步过程自发引发肿瘤形成。该模型与人类致癌作用的相似性使其成为研究 HNSCC 从癌前病变起始和进展的理想临床前平台。主要缺点是这些模型耗时且与人类癌症一样,在时间、位置和病变数量方面不可预测。GEMM 涉及具有基因修饰的转基因和敲除小鼠,导致肿瘤微环境中的恶性转化,体内重现肿瘤发生,包括它们与免疫系统的相互作用。然而,当转化为临床研究时,大多数 HNSCC GEMM 的肿瘤发生率低且预后意义有限。移植小鼠模型由于其一致性、可用性和效率而成为癌症研究中最广泛使用的模型。根据供体和受体物种的匹配情况,移植小鼠模型可分为异种移植和同基因模型。在后一种模型中,移植细胞和宿主来自同一品系,使得同基因模型与研究功能性免疫系统相关。在这篇综述中,我们全面总结了这些不同 HNSCC 小鼠模型的特征、建立方法和潜在应用,旨在帮助研究人员为其研究选择合适的动物模型。