Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.
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DOI:
10.1038/sj.bjc.6602325
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发表时间:
2005-02-14
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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前列腺癌具有通过尚未表征的机制转移到骨髓基质(BMS)的倾向。我们已经定义了一系列的共培养模型的入侵,模拟血液/BMS的边界,并允许阐明的信号和力学的跨内皮细胞迁移内的复杂的骨髓环境。共聚焦显微镜显示前列腺上皮细胞特异性结合骨髓内皮细胞-内皮细胞连接并启动内皮细胞收缩。跨内皮迁移通过上皮细胞伪足过程进行,在232±43分钟后发生完全上皮迁移。基质衍生因子-1(SDF-1)/CXCR 4信号转导诱导PC-3穿过基底膜侵入,尽管侵入水平比对BMS(P=0.0007)或骨髓内皮细胞(P=0.004)的侵入低3.5倍。10 μM SDF-1抑制剂T140可完全抑制最大SDF-1侵袭信号传导。然而,10 μM T140仅分别使对BMS和骨髓内皮细胞的侵袭减少59%(P=0.001)和29%(P=0.011)。这项研究强调了研究信号分子和/或抑制剂的潜在作用的必要性,不仅在单细胞模型中,而且在模拟骨髓复杂环境的共培养模型中。
Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232±43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 μM of the SDF-1 inhibitor T140. However, 10 μM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow.
巨核细胞对基质细胞衍生因子1(SDF-1)的跨内皮迁移增强了血小板的形成。
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