Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Vet Comp Oncol. 2011 Sep;9(3):207-18. doi: 10.1111/j.1476-5829.2010.00249.x. Epub 2010 Dec 14.
The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.
转移的发展是骨肉瘤（OS）犬科和人类患者死亡的最主要原因。Ezrin 与人类、犬科和鼠类骨肉瘤的肿瘤进展和转移有关。在人类和鼠类骨肉瘤的转移进展过程中，Ezrin 的激活受到蛋白激酶 C（PKC）的动态调控。为了在针对 Ezrin 生物学的治疗方法的开发中纳入犬科动物，我们对四种新的犬科骨肉瘤细胞系进行了表征，并在这些细胞中证实了 PKC 和 Ezrin 之间的关系。四条细胞系中的三条在小鼠中形成了肿瘤，其组织学与骨肉瘤一致。所有细胞系均明显为非整倍体，表达 Ezrin 和 PKC。最后，使用 PKC 抑制剂抑制 Ezrin 磷酸化和细胞迁移。这些数据表明，PKC 介导的 Ezrin 激活与犬科骨肉瘤细胞的转移表型之间存在关联。
