Ortiz Angelica, Lin Sue-Hwa
Department of Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Recent Results Cancer Res. 2012;192:225-33. doi: 10.1007/978-3-642-21892-7_11.
Normal bone development and maintenance are sustained through a balanced communication between osteoclasts and osteoblasts. Invasion of the bone compartment by cancer cells causes an imbalance in their activities and results in predominantly bone lysing or bone forming phenotypes depending on the origin of the cancer. Tumor-induced bone lesions usually exhibit disturbances of both cell types. Thus, osteoclast activity is activated in a predominantly osteoblastic lesion and vice versa. These cancer-induced bone responses favor the survival and growth of cancer cells in their new environment. Therapies that can restore the balance may limit the growth of cancer cells in the bone. The recent development of agents that target the osteolytic components of bone metastasis, including bisphosphonates and denosumab, showed promising results in osteolytic bone diseases such as multiple myeloma but were less effective in improving the osteoblastic bone disease found in prostate cancer. Thus, while osteolytic components are present in both osteoblastic and osteolytic bone lesions, inhibition of the osteolytic component is not sufficient to alter the vicious cycle leading to tumors with an osteoblastic phenotype. These observations suggest that osteolytic and osteoblastic bone metastases are not the same and tumor-induced osteoblastic and osteolytic activity play different roles in supporting their growth and survival.
正常的骨骼发育和维持通过破骨细胞与成骨细胞之间的平衡交流得以维系。癌细胞侵入骨腔会导致它们的活动失衡，并根据癌症的起源导致主要为溶骨性或成骨性表型。肿瘤诱导的骨病变通常表现出两种细胞类型的紊乱。因此，在主要为成骨性的病变中破骨细胞活性被激活，反之亦然。这些癌症诱导的骨反应有利于癌细胞在其新环境中的存活和生长。能够恢复平衡的疗法可能会限制癌细胞在骨中的生长。最近开发的针对骨转移溶骨成分的药物，包括双膦酸盐和地诺单抗，在溶骨性骨疾病如多发性骨髓瘤中显示出有前景的结果，但在改善前列腺癌中的成骨性骨疾病方面效果较差。因此，虽然成骨性和溶骨性骨病变中都存在溶骨成分，但抑制溶骨成分不足以改变导致具有成骨性表型肿瘤的恶性循环。这些观察结果表明，成骨性和溶骨性骨转移并不相同，肿瘤诱导的成骨和溶骨活性在支持它们的生长和存活中发挥不同的作用。
