Croset Martine, Kan Casina, Clézardin Philippe
INSERM, UMR 1033 , Lyon, France ; Faculté Médecine RTH Laennec, University of Lyon , Villeurbanne, France.
Bonekey Rep. 2015 May 13;4:688. doi: 10.1038/bonekey.2015.56. eCollection 2015.
Skeletal metastases are complications of epithelial cancers, among which breast, prostate and lung carcinomas are the most osteotropic. In primary tumours, a subset of cancer cells undergoes epithelial-mesenchymal transition, acquires mobility to migrate into the surrounding stroma and seeds at distant sites to grow. The specific development of bone metastasis requires the recruitment of circulating tumour cells in the bone marrow, their adaptation to survive in the surrounding microenvironment where they alter the functions of osteoclasts and osteoblasts, and hijack signals coming from the bone matrix. Each of the molecular pathways underlining these steps is regulated by multiple factors, through the tight control of genes expressed by cancer cells interacting with cells from the bone microenvironment. In this context, miRNAs can act as master regulators of gene expression to control multiple aspects of bone metastasis formation, including cancer cell escape from the primary tumour site, cancer cell dissemination to bone and invasion of the bone marrow, as well as secondary outgrowth and tumour-stroma cell interactions. In the clinic, specific miRNA signatures have been identified in osteotropic cancer cells, raising the possibility that miRNAs could be used as biomarkers of bone metastasis. The regulatory activity of miRNAs in the bone microenvironment also suggests that miRNAs could be promising therapeutic targets.
骨转移是上皮癌的并发症，其中乳腺癌、前列腺癌和肺癌最易发生骨转移。在原发性肿瘤中，一部分癌细胞会经历上皮-间质转化，获得迁移到周围基质并在远处位点播种生长的能力。骨转移的具体发展过程需要募集骨髓中的循环肿瘤细胞，使其适应在周围微环境中生存，在此过程中它们会改变破骨细胞和成骨细胞的功能，并劫持来自骨基质的信号。这些步骤所涉及的每一条分子途径都受到多种因素的调控，通过对癌细胞与骨微环境中的细胞相互作用所表达的基因进行严格控制来实现。在这种情况下，微小RNA（miRNA）可作为基因表达的主要调节因子，控制骨转移形成的多个方面，包括癌细胞从原发性肿瘤部位逃逸、癌细胞向骨组织扩散并侵入骨髓，以及继发性肿瘤生长和肿瘤-基质细胞相互作用。在临床上，已在易发生骨转移的癌细胞中鉴定出特定的miRNA特征，这增加了miRNA可作为骨转移生物标志物的可能性。miRNA在骨微环境中的调节活性还表明，miRNA可能是很有前景的治疗靶点。
