Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Neoplasia. 2010 Feb;12(2):116-27. doi: 10.1593/neo.91384.
Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bone marrow. The role of the niche is thought to be the induction and sustenance of HSC dormancy. If metastatic PCa cells occupy a similar or the same ecological niche as HSCs, then it is likely that the initial role of the HSC niche will be to induce dormancy in metastatic cells. In this study, we demonstrate that the binding of PCa to annexin II induces the expression of the growth arrest-specific 6 (GAS6) receptors AXL, Sky, and Mer, which, in the hematopoietic system, induce dormancy. In addition, GAS6 produced by osteoblasts prevents PCa proliferation and protects PCa from chemotherapy-induced apoptosis. Our results suggest that the activation of GAS6 receptors on PCa in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy.
我们最近的研究表明，在成骨细胞表面表达的膜联蛋白 II 在造血干细胞 (HSCs) 与骨内膜龛的黏附中起着重要作用。同样，前列腺癌 (PCa) 细胞表达膜联蛋白 II 受体，似乎利用干细胞龛来归巢到骨髓。龛的作用被认为是诱导和维持 HSC 休眠。如果转移性 PCa 细胞占据与 HSCs 相似或相同的生态位，那么 HSC 龛的初始作用可能是诱导转移性细胞休眠。在这项研究中，我们证明了 PCa 与膜联蛋白 II 的结合诱导了生长停滞特异性 6 (GAS6) 受体 AXL、Sky 和 Mer 的表达，在造血系统中，这些受体诱导休眠。此外，成骨细胞产生的 GAS6 可阻止 PCa 增殖并保护 PCa 免受化疗诱导的细胞凋亡。我们的结果表明，骨髓环境中 PCa 上 GAS6 受体的激活可能作为一个分子开关发挥关键作用，建立转移性肿瘤细胞休眠。
