Bone metastasis: pathogenesis and therapeutic implications
Bone metastasis: pathogenesis and therapeutic implications
复制标题
DOI：
10.1007/s10585-007-9112-8
复制
发表时间：
2007-11-01
影响因子：
4
通讯作者：
Teti, Anna
中科院分区：
文献类型：
--
作者：
Clezardin, Philippe;Teti, Anna
晚期癌症容易转移。内脏转移更有可能是致命的，而仅转移到骨骼的患者可以存活长达10年或更长时间。然而，骨转移的有效治疗方法尚不存在，双膦酸盐改善了生活质量，但没有延长生命的益处。根据骨细胞类型的不同，骨转移可分为溶骨性、骨硬化性或混合性病变。这两种情况都会导致高发病率，并显著增加病理性骨折的风险。几种分子机制导致癌细胞转移到骨，而嗜骨性癌细胞被认为获得骨细胞样特性，从而改善骨微环境中的归巢、粘附、增殖和存活。骨细胞伪表型的获得，称为骨模仿，可能依赖于成骨细胞和破骨细胞基因的表达，因此需要多基因程序。几个微环境因素提高了癌细胞在骨骼部位的发展能力，并且相互有害的刺激在肿瘤细胞和居住在骨骼环境中的细胞之间产生了恶性循环。干细胞生态位对骨转移的发展和肿瘤休眠现象的影响目前只是推测。肿瘤休眠现象允许肿瘤细胞在形成明显病变之前保持数十年的静止状态。然而，已知维持造血干细胞群处于静止状态的成骨细胞生态位可能参与骨转移的发展，这一前景广阔的研究领域正在迅速扩大。
Advanced cancers are prone to metastasize. Visceral metastases are more likely to be fatal, while patients with only metastases to bone can survive up to 10 years or more. However, effective treatments for bone metastases are not yet available and bisphosphonates improve the quality of life with no life-prolonging benefits. Bone metastases are classified as osteolytic, osteosclerotic or mixed lesions according to the bone cell types more prominently involved. Either conditions induce high morbidity and dramatically increase the risk of pathological fractures. Several molecular mechanisms bring about cancer cells to metastasize to bone, and osteotropic cancer cells are believed to acquire bone cell-like properties which improve homing, adhesion, proliferation and survival in the bone microenvironment. The acquisition of a bone cell pseudo-phenotype, denominated osteomimicry, is likely to rely on expression of osteoblastic and osteoclastic genes, thus requiring a multigenic programme. Several microenvironmental factors improve the ability of cancer cells to develop at skeletal sites, and a reciprocal deleterious stimulation generates a vicious cycle between the tumour cells and the cells residing in the bone environment. The impact of the stem cell niche in the development of bone metastases and in the phenomenon of tumour dormancy, that allows tumour cells to remain quiescent for decades before establishing overt lesions, is at present only speculative. However, the osteoblast niche, known to maintain the haematopoietic stem cell population in a quiescent status, is likely to be involved in the development of bone metastases and this promising research field is rapidly expanding.