Understanding genetic progression of squamous cell carcinoma to spindle cell carcinoma in a mouse model of head and neck cancer.

Reports have suggested that spindle cell carcinoma of the head and neck occurs following radiation therapy of incompletely resected SCC, representing anaplastic progression of the primary tumor. Examination of differences between spindle cell carcinoma and SCC may provide important information about anaplastic progression, clinical behavior, and response to therapy. We created a mouse model that developed spindle cell carcinoma. Spindle cell carcinoma was characterized by marked downregulation of epithelial differentiation markers and cell adhesion genes. Expression of growth factors and receptors important for epithelial proliferation was inhibited while those which regulate fibroblast and mesenchymal cell proliferation were increased. By far the largest class of upregulated genes in spindle cell carcinomas was chemokine receptors and ligands which are involved in tumor cell invasion and metastasis. These changes in gene expression clearly show loss of epithelial characteristics, acquisition of mesenchymal phenotypes, and increased propensity for invasion and metastasis by spindle cell carcinomas.