Orthotopic xenograft model of cervical cancer for studying microenvironmental effects on metastasis formation and response to drug treatment.

Cancers arising in the uterine cervix are usually squamous cell carcinomas that develop from preneoplastic lesions. They invade locally, and then typically metastasize to the regional lymph nodes and eventually to distant sites. Orthotopically grown xenografts are technically challenging to perform, but recapitulate the clinical situation to a greater extent than xenografts grown at subcutaneous or intramuscular sites. Thus, orthotopic xenografts develop lymphovascular invasion and metastasize to the para-aortic lymphatic chain in a pattern similar to that seen in patients. The extent of (lymph node) metastases is particularly apparent when the implanted tumor cells are transfected to express a fluorescent marker, such as DsRed, which allows the exposed retroperitoneum to be examined by fluorescence microscopy. Described in this unit is a surgical technique for orthotopic implantation and the use of this model for investigating the effects of novel agents as inhibitors of tumor growth and metastasis.