A mouse fibroblast cell model to study human papillomavirus-associated tumorigenesis

Cervical cancer represents the second most common cancer in women worldwide. About 90% of cervical cancer contain high-risk human papillomavirus (HPV) DNA, most often HPV type 16. Animal models and mostly laboratory mice are excellent for carrying out diverse immunological studies. We transfected a fibroblast cell line, 3T3-A31, with human papillomavirus type 16 genome to develop an in vivo/in vitro malignant transformant model. Isolated clones inoculated to immunocompetent mice displayed a tumorigenic phenotype. Small clusters of metastatic cells were found in the liver of animal 45 days after receiving the inoculum. Integrated viral DNA and expression of E7 viral oncogene from the high-risk HPV-16 were demonstrated both in transfectans and tumor-derived cells. The observed high-grade neovascularization was correlated with the upregulation of vascular endothelial growth factor (VEGF) mRNA on HPV-16 transformed fibroblast cells. These observations emphasize the association between papillomavirus expression and progression to malignancy.