Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis.
Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian-specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian-specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF-LC-AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN-45, KATO-III, and RERF-LC-AI) metastasized to the ovary. We compared E-cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E-cadherin down-regulation and others did not. E-cadherin was then forcibly expressed in RERF-LC-AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E-cadherin expression. We also performed histological investigation of clinical ovarian-metastatic tumor cases. About half of all ovarian-metastatic tumor cases showed loss or reduction of E-cadherin expression. These data suggest that E-cadherin down-regulation may be involved in ovarian-specific metastasis.
Kuwabara
Yoshiko
Y
Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Yamada
Taketo
T
Yamazaki
Ken
K
Du
Wen-Lin
WL
Banno
Kouji
K
Aoki
Daisuke
D
Sakamoto
Michiie
M
D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D015820:Cadherins