Mechanisms of osteolytic bone metastases in breast carcinoma
Mechanisms of osteolytic bone metastases in breast carcinoma
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DOI：
10.1002/cncr.11132
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发表时间：
2003-02-01
期刊：
影响因子：
6.2
通讯作者：
Mundy, GR
中科院分区：
文献类型：
--
作者：
Käkönen, SM;Mundy, GR
溶骨性和成骨性转移通常是晚期前列腺癌和乳腺癌患者发病率较高的原因。乳腺癌发生骨转移是因为骨为转移性癌细胞的侵袭行为提供了有利的部位。癌细胞和骨微环境之间出现恶性循环，这是由生长因子的产生介导的，例如骨中的转化生长因子β和胰岛素生长因子以及肿瘤细胞产生的甲状旁腺激素相关蛋白（PTHrP）。骨质溶解和肿瘤细胞积累可以通过抑制任何这些肢体的恶性循环来中断。例如，双膦酸盐（例如帕米膦酸盐、伊班膦酸盐、利塞膦酸盐、氯膦酸盐和唑来膦酸盐）在乳腺癌转移的实验模型中抑制骨损伤和骨中的肿瘤细胞负荷。 PTHrP 中和抗体可抑制 PTHrP 对破骨细胞骨吸收的影响，还可减少溶骨性骨病变和骨中的肿瘤负荷。其他抑制骨微环境中乳腺癌细胞产生的 PTHrP 的药理学方法也产生类似的有益效果。识别导致溶骨转移的分子机制对于设计针对这种破坏性并发症的有效疗法至关重要。 (C) 2003 年美国癌症协会。
Osteolytic and osteoblastic metastases are often the cause of considerable morbidity in patients with advanced prostate and breast carcinoma. Breast carcinoma metastasis to bone occurs because bone provides a favorable site for aggressive behavior of metastatic cancer cells. A vicious cycle arises between cancer cells and the bone micro environment, which is mediated by the production of growth factors such as transforming growth factor beta and insulin growth factor from bone and parathyroid hormone-related protein (PTHrP) produced by tumor cells. Osteolysis and tumor cell accumulation can be interrupted by inhibiting any of these limbs of the vicious cycle. For example, bisphosphonates (e.g., pamidronate, ibandronate, risedronate, clodronate, and zoledronate) inhibit both bone lesions and tumor cell burden in bone in experimental models of breast carcinomametastasis. Neutralizing antibodies to PTHrP, which inhibit PTHrP effects on osteoclastic bone resorption, also reduce osteolytic bone lesions and tumor burden in bone. Other pharmacologic approaches to inhibit PTHrP produced by breast carcinoma cells in the bone microenvironment also produce similar beneficial effects. Identification of the molecular mechanisms responsible for osteolytic metastases is crucial in designing effective therapy for this devastating complication. (C) 2003 American Cancer Society.