2 DISTINCT PATTERNS OF PERITONEAL INVOLVEMENT SHOWN BY IN-VITRO AND IN-VIVO OVARIAN-CANCER DISSEMINATION MODELS

We established an in vitro peritoneal dissemination model using six ov arian cancer cell lines and cultured mesothelial cells. Ovarian cancer cells were classified into two types, invasive or adhesive, on the ba sis of their interaction with the mesothelial cell. monolayer. The ova rian cancer cell lines derived from mucinous cystadenocarcinoma, poorl y differentiated adenocarcinoma and undifferentiated carcinoma, which belonged to the invasive type, began to invade beneath the mesothelial monolayer from several hours after seeding in vitro, expelling the me sothelial cells at the periphery and forming colonies directly on the dish surface. On the other hand, cancer cell lines of clear cell carci noma, which belonged to the adhesive type, showed colony formation wit h adhesion on the mesothelial monolayer even 18 h after seeding. Invas ive-type cell lines invaded into the mesothelial monolayer at various rates in vitro, and the degree of invasiveness showed good correlation with the degree of peritoneal dissemination in vivo after intraperito neal injection of cancer cells into nude mice. Adhesive-type cells sho wed rather higher dissemination rates in vivo. Microscopic observation of in vivo peritoneal dissemination at one day after inoculation also revealed two patterns of peritoneal involvement similar to those in v itro. In the in vitro model, anti-integrin alpha 2- and beta 1-antibod ies inhibited the infiltration of invasive-type cells into the mesothe lial monolayer, but did not affect colony formation by adhesive-type c ells on the monolayer, indicating that invasion by both cell types was mediated by different molecules. This in vitro model is thought to be useful for analysis of the molecular mechanisms of peritoneal dissemi nation.