Mouse Models for Head and Neck Squamous Cell Carcinoma.

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.

Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis.

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising of normal and malignant squamous epithelium, were generated and contributed to the Head and Neck Cancer Genome Anatomy Project (HN-CGAP). Initial analysis of the sequence information indicated the existence of many novel genes in these libraries [Oral Oncol 36 (2000) 474]. In this study, we surveyed the available sequence information using bioinformatic tools and identified a number of known genes that were differentially expressed in normal and malignant epithelium. Furthermore, this effort resulted in the identification of 168 novel genes. Comparison of these clones to the human genome identified clusters in loci that were not previously recognized as being altered in HNSCC. To begin addressing which of these novel genes are frequently expressed in HNSCC, their DNA was used to construct an oral-cancer-specific microarray, which was used to hybridize alpha-(33)P dCTP labeled cDNA derived from five HNSCC patient sets. Initial assessment demonstrated 10 clones to be highly expressed (>2-fold) in the normal squamous epithelium, while 14 were highly represented in the malignant counterpart, in three of the five patient sets, thus suggesting that a subset of these newly discovered transcripts might be highly expressed in this tumor type. These efforts, together with other multi-institutional genomic and proteomic initiatives are expected to contribute to the complete understanding of the molecular pathogenesis of HNSCCs, thus helping to identify new markers for the early detection of preneoplastic lesions and novel targets for pharmacological intervention in this disease.

Alterations of p53, pRb, cyclin D(1) and cdk4 in human oral and pharyngeal squamous cell carcinomas.

Alteration of expression of tumour suppressor genes and cell cycle regulators may be responsible for oral and pharyngeal cancer development. We have studied the expression of p53, pRb, cyclin D(1) and cdk4 in 53 cases of oral and pharyngeal squamous cell carcinomas using immunohistochemistry. Tumour expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei. Positive p53 expression was detected in 27/53 (50.94%) cases. Lack of pRb immunostaining was observed in 39/53 (73.58%) cases. Overexpression of cyclin D(1) was shown in 21 (39.62%) tumours. The overexpression of cdk4 was detected in 43/53 (81.13%) cases. There was no significant association among these cell cycle regulatory proteins. This implies that the aberration of an important cell cycle regulator may be sufficient to disrupt regulatory mechanism in a manner favouring tumourigenesis. In summary, our results suggest that inappropriate expression of p53, pRb, cyclin D(1) or cdk4 is likely to contribute to the development of oral and pharyngeal cancers. The lack of pRb expression and/or overexpression of cdk4 play a crucial role in the development of this malignancy.