Metastatic phenotype in murine cells transfected with human DNA.

DNAs of cell lines derived from human metastatic tumors were transfected into tumorigenic, nonmetastasizing murine cells (BALB 3T12-3) to determine if the capacity to metastasize could be conferred by this transfer of portions of the human genome. Using the calcium phosphate method, whole cell DNA was cotransfected into the murine cells along with a neomycin-resistance gene. Recipient murine cells (10(6] which grew in neomycin, indicating successful transfection, were injected via tail vein into 4- to 6-week-old male athymic nude mice. Animals were sacrificed if they appeared ill or at times up to 24 weeks after injection if they remained healthy. Murine cells transfected with DNA from one cell line derived from a hepatic metastasis of a human pancreatic adenocarcinoma (NCI-ZRY) formed experimental pulmonary metastases in 11 of 13 animals injected. Neither murine cells (unmanipulated BALB 3T12-3 cells) nor murine cells transfected with DNA from the same cell type (BALB 3T12-3 cells transfected with BALB 3T12-3 DNA) produced experimental metastases when each cell type was injected into 20 and 10 animals, respectively (P2 less than 0.0001). The results are consistent with the hypothesis that expression of a structural or regulatory protein encoded on human DNA conferred the metastatic phenotype to the recipient murine cells.