AbstractIn the course of development of an in vivo invasion model, sublines of a series of allogeneic and isogeneic carcinoma cell lines have been selected that show enhanced invasion of the peritoneum. It was found that, during the proliferation of tumor cell lines in ascitic form in the abdominal cavity, small numbers of cells infiltrated or firmly adhered to the peritoneum in at least 8/12 of the tumor-host combinations tried. After thorough washing of the peritoneum it was disaggregated by an enzyme mixture, and the resulting mixture of normal and tumor cells was inoculated intraperitoneally. Peritoneal isolations were made serially for 3 to 12 times. In 6 of 8 cases where the isolation produced a stable ascites, the cells showed enhanced peritoneal invasion compared with the parent cell line. The invasion of some of the cell lines was tested in another invasion model consisting of cultured mouse buccal mucosa (9/10 cell lines invaded the explant). In 3/3 cell lines showing enhanced peritoneum invasion in vivo, there was no enhanced invasion of the buccal mucosa. The enhanced peritoneum invasion appears to be tissue specific rather than a general increase in invasion potential. Pairs of high-and low-invasive cell lines were obtained that should be useful for screening for invasion modulating agents using the mouse ascites/peritoneum in vivo model. It is suggested that the method might be generalized to produce various tumor cell lines that target for the normal tissues that are adjacent to proliferating solid or circulating tumors.