title: An orthotopic nude mouse model of oral tongue squamous cell carcinoma.
abstract: OBJECTIVE
  Despite advances in our understanding, prevention, and treatment of head and neck squamous cell carcinoma (SCC), the 5-year survival rates for patients remain low. This poor prognosis for head and neck SCC and SCC of the oral tongue (SCCOT) in particular reflects a limited understanding of the mechanisms of local and regional metastasis, which accounts for a majority of deaths. To analyze the molecular and cellular mechanisms of metastasis, we have developed an orthotopic nude mouse model of SCCOT.
  
  
  METHODS
  Nude mice were injected submucosally in the tongue or subcutis with human squamous cell carcinoma of the oral cavity cell lines Tu159, Tu167, and MDA1986. The mice were necropsied and examined for the presence of primary tumors, and regional and systemic metastases.
  
  
  RESULTS
  For all three of the squamous cell carcinoma of the oral cavity cell lines, tumors developed more readily in the orthotopic site, the tongue, than in the ectopic subcutis. MDA1986 cells were highly tumorigenic, particularly at the orthotopic site, with as few as 5 x 10(3) cells producing tumors in all of the mice. In contrast, s.c. tumor formation required at least 1 x 10(5) cells. The tumorigenicity observed between those mice given submucosal inoculation and those mice given s.c. inoculation (P < 0.0001). Regional metastases initially occurred in <10% of mice. To generate tumor lines of increased metastatic potential, regional metastases were isolated from cervical lymph nodes after the development of orthotopic tongue tumors. Serial passage of these lymph nodes resulted in a cell line more metastatic than its parental line. When injected into the tongues of mice, these cells metastasized to regional lymph nodes in 30% of mice and to the lungs in 20%.
  
  
  CONCLUSIONS
  In this orthotopic murine model, oral tongue cancer recapitulates the behavior of human SCCOT, allowing for detailed studies of its biology and therapy.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. jmyers@mdanderson.org
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Holsinger
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D006801:Humans; D007279:Injections, Subcutaneous; D008164:Luminescent Proteins / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins