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 t...

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Published in:Cancer science 2008-10, Vol.99 (10), p.1933-1939
Main Authors: Kuwabara, Yoshiko, Yamada, Taketo, Yamazaki, Ken, Du, Wen‐Lin, Banno, Kouji, Aoki, Daisuke, Sakamoto, Michiie
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cadherins - genetics
Cadherins - metabolism
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cell Line, Tumor
Disease Models, Animal
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Medical sciences
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Metastasis
Original
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Tumors
Xenograft Model Antitumor Assays
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Summary: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. (Cancer Sci 2008; 99: 1933–1939)
ISSN:1347-9032
1349-7006
1349-7006
DOI:10.1111/j.1349-7006.2008.00946.x