Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells.
In a previous study, we demonstrated that calponin h1 suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16-F10 melanoma (F10) cells was more extensive in calponin h1-deficient (CN(-/-)) mice with fragility of mesothelial (MS) cells than in their calponin h1-wild (CN(+/+)) counterparts. In our study, we assessed the therapeutic effect of calponin h1 on peritoneal dissemination. F10 cells were overlaid on the cultured CN(+/+) or CN(-/-) MS cells and the effect of calponin h1 on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin h1 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 h1 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 F10 cells. Peritoneal dissemination was prominently suppressed in AdGFP-CN-infected CN(-/-) mice, and the survival of those mice was significantly prolonged. Thus, calponin h1 functioned to protect host MS cells from the invasion of F10 cells.
Hashimoto
Shigenari
S
Department of Molecular Oncology, Division of Molecular and Cellular Biology, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Takeoka
Michiko
M
Taniguchi
Shun'ichiro
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000627:therapeutic use*; D002478:Cells, Cultured; D015536:Down-Regulation; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D015316:Genetic Therapy; D007124:Immunoenzyme Techniques; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009360:Neoplastic Cells, Circulating; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D010537:Peritoneum / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000096985:Calponins
D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D000096985:Calponins