Clinically relevant oral cancer model for serum proteomic eavesdropping on the tumour microenvironment

Background: Serum proteomics has enormous potential in the identification of biomarkers and the development of new therapies for oral cancer. Current efforts are limited by the lack of a control subject. The human-mouse chimeric model offers a solution. Objectives: To develop and test two orthotopic xenograft mouse models of human oral squamous cell carcinoma for research in serum proteomics. Methods: Advanced human oral cancer from three patients was implanted orthotopically into the tongues of 19 SCID and 4 RAG2/gamma(c) knockout (KO) mice. Adjacent normal tissue from each patient was also implanted into nine SCID and 4 RAG2/gamma(c) KO mice. The models were compared for tissue take, the presence of metastasis, and histologic invasiveness. Mouse serum was preserved for studies in serum proteomics. Results: Tumour tissue was successfully implanted into SCID and RAG2/gamma(c) mice, and the invasiveness was confirmed pathologically. Three of the control mice demonstrated the persistence of normal tissue more than 1 month after implantation. This is the first time that this has been reported. The larger size of the RAG2/gamma(c) KO mouse facilitated serum collection for serum proteomics. Conclusions: Both RAG2/gamma(c) KO and SCID mouse are able to reliably engraft human oral cancer. Engraftment of normal oral tissue was less reliable. This is the first in vivo model allowing identification of proteins released from the turnout microenvironment.