A novel experimental mouse model of peritoneal dissemination of human gastric cancer cells: Different mechanisms in peritoneal dissemination and hematogenous metastasis

We established a new cell line, AZ-P7a, with high peritoneal-metastatic pot ential in nude mice. AZ-P7a cells were derived from the human gastric carci noma line AZ-521, which has low capacity for peritoneal dissemination. AZ-P 7a cells developed peritoneal metastasis in 11/14 (78.6%) mice, whereas the parental AZ-521 cells developed metastasis in 2/6 (33.3%) mice. The metast atic foci in the peritoneum showed essentially the same histological appear ance as those induced by parental cells. The tumorigenicity and the motile activity of AZ-P7a cells were stronger than those of the parental AZ-521 ce lls; in contrast, adhesion to the extracellular matrix and the production o f vascular endothelial growth factor by AZ-P7a cells were decreased. In flu orescence-activated cell sorter (FACS) analysis, AZ-P7a cells expressed sig nificantly greater levels of integrins alpha 2, alpha 3, alpha 5, alpha 6 a nd alpha v beta 5, as compared with AZ-521 cells. However, alpha 1, alpha 4 , alpha v beta 3, hCD44H, hCD44v3, hCD44v6 and hCD44v10 were not expressed in either cell line. AZ-P7a cells developed no liver metastasis when admini stered by the intrasplenic injection method, though the highly liver metast atic cell line AZ-H5c showed the same rate of peritoneal dissemination as t hat exhibited by AZ-P7a cells after intraabdominal injection. These finding s suggested that the mechanism of peritoneal dissemination differed from th at of hematogenous metastasis. Moreover, the latter appears to be controlle d by more complex mechanisms than the former. Thus, this cell line might be useful for investigating the mechanism of peritoneal dissemination of huma n gastric cancer.