Ivan Vičić, Department of Oncology, University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia,
Croat Med J. 2021 Jun 30;62(3):270-282. doi: 10.3325/cmj.2021.62.270.
Owing to its frequent occurrence and severe clinical picture, bone metastasis is an important problem in the clinical course of tumor diseases. Bone metastasis develops when the physiological remodeling process is disrupted by tumor cells via the same molecular mechanisms used by native bone cells. The process includes molecular crosstalk between osteocytes and osteoblasts and osteoclasts. Osteolytic bone metastasis, most often seen in breast cancer, is characterized by promoted differentiation and function of osteoclasts and reduced osteoblast function. Tumor cells take advantage of factors released by bone tissue resorption, thus establishing a vicious cycle that promotes the metastatic process. In osteoblastic metastasis, most often seen in prostate cancer, osteoblast function and differentiation are promoted, while osteoclast activity is reduced, resulting in net gain of bone tissue. Mechanisms involved in the early stages of bone metastasis and cancer cell dormancy have been understudied, and their exploration may pave the way for potential therapeutic strategies. Tumor affects the bone marrow microenvironment via exosomes, soluble factors, and membrane-bound ligands. In this way, an initial lesion is established, which after a variable duration of disseminated tumor cells dormancy progresses to an overt condition. The current review deals with basic mechanisms involved in bone metastasis formation and propagation. We illustrated a disparity between the diversity and number of factors included in the disease pathophysiology and the number of available and developing therapeutic options. We also examined new therapeutic strategies affecting molecular pathways.
由于其频繁发生和严重的临床表现，骨转移是肿瘤疾病临床过程中的一个重要问题。当肿瘤细胞通过与天然骨细胞相同的分子机制破坏生理重塑过程时，就会发生骨转移。该过程包括成骨细胞、破骨细胞和骨细胞之间的分子相互作用。溶骨性骨转移最常发生于乳腺癌，其特征是破骨细胞的分化和功能增强，而成骨细胞的功能降低。肿瘤细胞利用骨组织吸收释放的因子，从而建立一个促进转移过程的恶性循环。在成骨性骨转移中，最常发生于前列腺癌，成骨细胞的功能和分化被促进，而破骨细胞的活性降低，导致骨组织净增加。骨转移和肿瘤细胞休眠的早期机制研究不足，对其探索可能为潜在的治疗策略铺平道路。肿瘤通过外泌体、可溶性因子和膜结合配体影响骨髓微环境。通过这种方式，建立了一个初始病变，经过一定时间的播散性肿瘤细胞休眠后，进展为明显的状态。本综述涉及骨转移形成和传播的基本机制。我们说明了疾病病理生理学中包含的因素的多样性和数量与现有和正在开发的治疗选择数量之间的差异。我们还研究了影响分子途径的新治疗策略。
