Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis
Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis
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DOI：
10.1111/j.1349-7006.2008.00946.x
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发表时间：
2008-10-01
期刊：
影响因子：
5.7
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Kuwabara, Yoshiko;Yamada, Taketo;Sakamoto, Michiie
卵巢转移病例的临床观察表明，卵巢特异性转移可能存在独特的机制。本研究旨在建立卵巢转移的动物模型，探讨卵巢特异性转移的机制。我们研究了卵巢转移的能力，在8个不同的人类癌细胞系的植入雌性NOD/SCID小鼠transnodal和腹腔内。经静脉接种，只有RERF-LC-AI，一种低分化癌细胞系，经常表现出卵巢转移。通过腹膜内接种，八个细胞系中的四个（HGC 27、MKN-45、KATO-III和RERF-LC-AI）转移到卵巢。我们比较了卵巢转移细胞系和其他细胞系中E-钙粘蛋白的表达。所有这四个卵巢转移细胞系和HSKTC，一个Krukenberg肿瘤细胞系，显示E-cadherin下调和其他没有。E-cadherin在RERF-LC-AI中的强表达可完全抑制卵巢转移。转移到其他器官的能力不受E-钙粘蛋白表达的影响。我们还进行了临床卵巢转移性肿瘤病例的组织学研究。大约一半的卵巢转移性肿瘤病例显示E-cadherin表达缺失或减少。这些数据表明，E-cadherin下调可能参与卵巢特异性转移。（Cancer Sci 2008; 99：1933-1939）
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)