Animal Models of Oral Cancer Invasion
“Animal Models of Oral Cancer Invasion”
Tissue-specific orthotopic models of HNSCC have been challenging to produce due to a number of factors, including shared tissue specificity with the epithelium in the integument and esophagus, as well as the unique difficulties of studying tumor progression within the craniofacial region in live animals. We have adapted several common models in the field in order to generate systems that allow for effective initiation and study of HNSCC tumor invasion and regional metastasis similar to what is encountered in the clinic. Current models incorporate inducible genetic deletion (“knockout”) or forced transgenic overexpression of invasion-promoting proteins in the tongue epithelium driven by promoter elements active in the oral cavity. Carcinogenic induction of oral tumors in these models allows for the analysis of specific genes and their impact oral cancer invasion in tumors arising from the native epithelium. Additional models utilize direct injection of human tumor cell lines with altered expression of invasion-inducing genes into oral cavity tissues, followed by in vivo monitoring of tumor invasion and metastatic dissemination (see Project 3).
Mouse models of HNSCC commonly used in the lab. Left; Whole mount section of a resected tongue from a C57BL/6 mouse exposed to drinking water containing 50 µg/ml of carcinogen 4-nitroquinoline 1-oxide (4-NQO) for eight weeks. In this instance, 4-NQO induced a tumor on the dorsal surface that invaded through the underlying striated muscle and breached the ventral lining mucosa. Non-viral oral squamous cell papillomas are indicated with asterisks. Epithelial cells were identified by immunostaining against cytokeratin 14. Right; Whole mount section of a resected mouse tongue harboring an orthotopic human HNSCC tumor. UMSCC1 HNSCC cells were injected into the tongue of an athymic nude mouse, forming a solid tumor after four weeks. Tumor visualization was achieved by staining the section with an anti-emmprin antibody to recognize human HNSCC. Bar = 100µm.
Figure and legend for the orthotopic tongue image was adapted from http://www.jove.com/video/2941/multi-photon-imaging-tumor-cell-invasion-an-orthotopic-mouse-model