Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro
Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro
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DOI：
10.1172/jci118841
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发表时间：
1996-08-01
影响因子：
15.9
通讯作者：
Papapoulos, S
中科院分区：
文献类型：
--
作者：
vanderPluijm, G;Vloedgraven, H;Papapoulos, S
双膦酸盐在乳腺癌患者骨骼并发症的治疗中的使用频率越来越高。在本文中，我们研究了双膦酸盐除了对肿瘤相关破骨细胞吸收的已知有益作用之外，是否能够抑制乳腺癌细胞与骨基质的粘附，为此，我们使用了两种体外骨基质模型（皮质骨切片和来自新生小鼠尾部的小梁骨的低温切片）。四种骨基质结合的含氮双膦酸盐（帕米膦酸盐、奥帕膦酸盐、阿仑膦酸盐和伊班膦酸盐）剂量依赖性地抑制乳腺癌细胞与骨的粘附和扩散，而依替膦酸盐和氯膦酸盐几乎没有作用或没有作用。引人注目的是，双膦酸盐抑制癌细胞与皮质骨和小梁骨粘附的效力的相对顺序与其体内相对抗吸收效力以及体外骨吸收测定中的排名相对应对其临床疗效具有预测价值。含氮双膦酸盐似乎选择性地改变细胞外骨基质的粘合特性，防止乳腺癌细胞附着在其上。除了双膦酸盐对肿瘤诱导的破骨细胞吸收的有益作用外，本文提出的先前未认识到的作用使这些药物适合对有骨转移风险的乳腺癌患者进行早期药物干预。
Bisphosphonates are used with increasing frequency in the management of skeletal complications in patients with breast cancer, In this paper, we have investigated whether bisphosphonates, besides their known beneficial effects on tumor-associated osteoclastic resorption, are capable of inhibiting breast cancer cell adhesion to bone matrix, For that we used two in vitro models for bone matrix (cortical bone slices and cryostat sections of trabecular bone from neonatal mouse tails).Four bone matrix-bound nitrogen-containing bisphosphonates (pamidronate, olpadronate, alendronate, and ibandronate) inhibited adhesion and spreading of breast cancer cells to bone dose-dependently, whereas etidronate and clodronate had little or no effect, Strikingly, the relative order of potency of the bisphosphonates in inhibiting the adhesion of cancer cells to cortical and trabecular bone corresponded to their relative antiresorptive potencies in vivo as well as their ranking in in vitro bone resorption assays with predictive value for their clinical efficacy. It appears that nitrogen-containing bisphosphonates alter selectively the adhesive properties of the extracellular bone matrix preventing the attachment of breast cancer cells to it.Besides the beneficial effects of bisphosphonates on tumor-induced osteoclastic resorption, the previously unrecognized effect presented in this paper makes these agents suitable for earlier pharmacologic intervention in patients with breast cancer at risk of developing bone metastases.