Shiozawa Yusuke, Havens Aaron M, Jung Younghun, Ziegler Anne M, Pedersen Elisabeth A, Wang Jingcheng, Wang Jianhua, Lu Ganwei, Roodman G David, Loberg Robert D, Pienta Kenneth J, Taichman Russell S
Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109-1078, USA.
J Cell Biochem. 2008 Oct 1;105(2):370-80. doi: 10.1002/jcb.21835.
One of the most life-threatening complications of prostate cancer is skeletal metastasis. In order to develop treatment for metastasis, it is important to understand its molecular mechanisms. Our work in this field has drawn parallels between hematopoietic stem cell and prostate cancer homing to the marrow. Our recent work demonstrated that annexin II expressed by osteoblasts and endothelial cells plays a critical role in niche selection. In this study, we demonstrate that annexin II and its receptor play a crucial role in establishing metastasis of prostate cancer. Prostate cancer cell lines migrate toward annexin II and the adhesion of prostate cancer to osteoblasts and endothelial cells was inhibited by annexin II. By blocking annexin II or its receptor in animal models, short-term and long-term localization of prostate cancers are limited. Annexin II may also facilitate the growth of prostate cancer in vitro and in vivo by the MAPK pathway. These data strongly suggest that annexin II and its receptor axis plays a central role in prostate cancer metastasis, and that prostate cancer utilize the hematopoietic stem cell homing mechanisms to gain access to the niche.
前列腺癌最危及生命的并发症之一是骨转移。为了开发针对转移的治疗方法，了解其分子机制很重要。我们在该领域的工作已将造血干细胞与前列腺癌归巢至骨髓的过程进行了类比。我们最近的研究表明，成骨细胞和内皮细胞表达的膜联蛋白II在微环境选择中起关键作用。在本研究中，我们证明膜联蛋白II及其受体在前列腺癌转移的建立中起关键作用。前列腺癌细胞系向膜联蛋白II迁移，且膜联蛋白II可抑制前列腺癌与成骨细胞和内皮细胞的黏附。通过在动物模型中阻断膜联蛋白II或其受体，前列腺癌的短期和长期定位受到限制。膜联蛋白II还可能通过丝裂原活化蛋白激酶（MAPK）途径促进前列腺癌在体外和体内的生长。这些数据有力地表明，膜联蛋白II及其受体轴在前列腺癌转移中起核心作用，且前列腺癌利用造血干细胞归巢机制进入微环境。
