Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells

In a previous study, we demonstrated that calponin hI suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16-F10 melanoma (F10) cells was more extensive in calponin hI-deficient (CN-/-) mice with fragility of mesothelial (MS) cells than in their calponin hI-wild (CN+/+) counterparts. In our study, we assessed the therapeutic effect of calponin h I on peritoneal dissemination. F10 cells were overlaid on the cultured CN+/+ or CN-/- MS cells and the effect of calponin hI on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin hI gene (AdGFP-CN) inserted was constructed and was applied to CN-/- MS cells or CN-/- mouse peritoneum to investigate its suppressive effect on the peritoneal dissemination caused by F10 cells. Greater retraction and invasion of F10 cells were observed in CN-/- MS than in CN+/+ cells in vitro, while down-regulation of calponin hI was observed in CN+/+ MS cells prior to the invasion of F10 cells. Infecting CN-/- MS cells with AdGFP-CN prevented their retraction and the invasion of F 10 cells. Peritoneal dissemination was prominently suppressed in AdGFP-CN-infected CN-/- mice, and the survival of those mice was significantly prolonged. Thus, calponin hI functioned to protect host MS cells from the invasion of F10 cells. (C) 2003 Wiley-Liss. Inc.