Abstract 333: Molecular and histologic characterization a patient-derived heterotransplant mouse model of head and neck squamous carcinoma.
Authors: Peng Shaohua , Creighton Chad , Zhang Yiqun , Sen Banibrata , Mazumdar Tuhina , Myers Jeffrey , Bell Diana , El-Naggar Adel , Williams Michelle , Johnson Faye 
Published: August 2014

Head and neck squamous cell carcinoma (HNSCC) is a deadly and disfiguring disease for which better systemic therapy is desperately needed. The development of new therapies for HNSCC and the understanding of its biology both depend upon clinically relevant animal models. An increasingly promising xenograft model, the heterotransplant model, is developed by surgically implanting tumor tissue directly from a patient into an immunocompromised mouse.

We have transplanted 30 HNSCC primary tumors from untreated patients directly into mice that included 27 tongue tumors, one maxillary gingival tumor, and two from the floor of the mouth. Five of 30 (17%) transplanted tumors could be serially passaged and used for therapeutic and mechanistic studies. One cell line has been established from a tongue primary.

Histopathologic characterization of our panel showed a concordance between xenografts (up to the tenth generation) and the corresponding patients’ tumors in terms of tumor differentiation, cancer cell appearance, necrosis, and keratin production.

To further characterize our model, we conducted gene expression analysis with Affymetrix U133A-microarrays on 20 patient tumors; 5 third generation and one tenth generation tumor in mice; one tumor-derived cell line; and 2 established cell lines (OSC19, Tu167). Although unsupervised clustering clearly separates patient tumors, xenografts, and cell lines into distinct groups, the early and late xenografts that were derived from the same patient clustered together. From the &gt;54,000 probes tested, there were 1417 probes that were distinct between the tumors growing in mice vs. the corresponding human tumors from which they were derived (p,0.01, fold change 1.4). There were 992 probes that were distinct between the human tumors that subsequently grew in mice vs. those that did not - suggesting that this model enriches for cancers with distinct biological features (p,0.01, fold change 1.4). We have successfully used one heterotransplant model for multiple studies of cancer drug efficacy.

Our results demonstrate the feasibility of a heterotransplant model of HNSCC. Although the gene expression patterns are distinct, the histology of the tumors in mice is similar to that of the same tumor in humans. Additionally, gene expression patterns and histology are relatively stable over multiple generations. Biologic gene pathways analysis for similarities and differences in this model will further refine the promise of heterotransplants as an in vivo model to test the efficacy of anti-cancer drugs.

This work was supported by R01-CA143369-01

Citation Format: Shaohua Peng, Chad Creighton, Yiqun Zhang, Banibrata Sen, Tuhina Mazumdar, Jeffrey Myers, Diana Bell, Adel El-Naggar, Michelle Williams, Faye Johnson. Molecular and histologic characterization a patient-derived heterotransplant mouse model of head and neck squamous carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 333. doi:10.1158/1538-7445.AM2013-333