Chu Khoi, Cheng Chien-Jui, Ye Xiangcang, Lee Yu-Chen, Zurita Amado J, Chen Dung-Tsa, Yu-Lee Li-Yuan, Zhang Sui, Yeh Edward T, Hu Mickey C-T, Logothetis Christopher J, Lin Sue-Hwa
Department of Genitourinary Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Mol Cancer Res. 2008 Aug;6(8):1259-67. doi: 10.1158/1541-7786.MCR-08-0077.
Bone is the most common site of metastases from prostate cancer. The mechanism by which prostate cancer cells metastasize to bone is not fully understood, but interactions between prostate cancer cells and bone cells are thought to initiate the colonization of metastatic cells at that site. Here, we show that cadherin-11 (also known as osteoblast-cadherin) was highly expressed in prostate cancer cell line derived from bone metastases and had strong homophilic binding to recombinant cadherin-11 in vitro. Down-regulation of cadherin-11 in bone metastasis-derived PC3 cells with cadherin-11-specific short hairpin RNA (PC3-shCad-11) significantly decreased the adhesion of those cells to cadherin-11 in vitro. In a mouse model of metastasis, intracardiac injection of PC3 cells led to metastasis of those cells to bone. However, the incidence of PC3 metastasis to bone in this model was reduced greatly when the expression of cadherin-11 by those cells was silenced. The clinical relevance of cadherin-11 in prostate cancer metastases was further studied by examining the expression of cadherin-11 in human prostate cancer specimens. Cadherin-11 was not expressed by normal prostate epithelial cells but was detected in prostate cancer, with its expression increasing from primary to metastatic disease in lymph nodes and especially bone. Cadherin-11 expression was not detected in metastatic lesions that occur in other organs. Collectively, these findings suggest that cadherin-11 is involved in the metastasis of prostate cancer cells to bone.
骨是前列腺癌转移最常见的部位。前列腺癌细胞转移至骨的机制尚未完全明确，但人们认为前列腺癌细胞与骨细胞之间的相互作用会促使转移细胞在该部位定植。在此，我们发现钙黏蛋白-11（也称为成骨细胞钙黏蛋白）在源自骨转移灶的前列腺癌细胞系中高表达，且在体外与重组钙黏蛋白-11具有强烈的同源性结合。用钙黏蛋白-11特异性短发夹RNA（PC3-shCad-11）下调源自骨转移灶的PC3细胞中钙黏蛋白-11的表达，显著降低了这些细胞在体外与钙黏蛋白-11的黏附。在转移小鼠模型中，经心内注射PC3细胞会导致这些细胞转移至骨。然而，当这些细胞中钙黏蛋白-11的表达被沉默时，该模型中PC3细胞转移至骨的发生率大幅降低。通过检测人前列腺癌标本中钙黏蛋白-11的表达，进一步研究了钙黏蛋白-11在前列腺癌转移中的临床相关性。正常前列腺上皮细胞不表达钙黏蛋白-11，但在前列腺癌中可检测到，其表达从原发性疾病到淋巴结尤其是骨转移疾病逐渐增加。在其他器官发生的转移病灶中未检测到钙黏蛋白-11的表达。总体而言，这些发现表明钙黏蛋白-11参与了前列腺癌细胞向骨的转移。
