Department of Gynecology and Obstetrics, Georg-August-University, Göttingen, Germany.
Int J Gynecol Cancer. 2014 Feb;24(2):210-7. doi: 10.1097/IGC.0000000000000050.
The cross talk between metastatic cancer cells and target sites is critical for the development and progression of metastases. Disruption of this interaction will allow to design mechanism-based effective and specific therapeutic interventions for metastases. We have established a coculture system of cells derived from different tumor entities and MG63 human osteoblastlike cells to analyze tumor cell invasion. Recently, we have shown that breast cancer cell invasion was dramatically increased when cocultured with MG63 cells.Using this model, we have now analyzed whether stromal-derived factor 1 (SDF-1) is responsible for human endometrial cancer cell invasion and whether kisspeptin-10 (KP-10) treatment affects SDF-1-induced invasion of endometrial cancer cells in vitro.
Invasion was quantified by assessment of endometrial cancer cell migration rate through an artificial basement membrane in a modified Boyden chamber during coculture with MG63 cells or after treatment with SDF-1α, SDF-1β, or the combination of both SDF-1 isoforms. In addition, the role of SDF-1 in invasion of endometrial cancer cells was analyzed by blocking SDF-1 secretion during coculture with MG64 cells. Furthermore, the effects of KP-10 treatment on MG63 coculture-driven and SDF-1-induced invasion were analyzed.
Endometrial cancer cell invasion was significantly increased when cocultured with MG63 cells. Treatment with KP-10 reduced the ability to invade a reconstituted basement membrane and to migrate in response to the cellular stimulus. This effect was significant in a dose window of 10(-13) to 10(-11) mol/L. During coculture, SDF-1 protein expression of MG63 cells was significantly increased. The MG63 coculture-induced increase of endometrial cancer cell invasion could be blocked by anti-SDF-1 antibodies. Treatment of endometrial cancer cells in monoculture (without MG63) with SDF-1α, SDF-1β, or the combination of both isoforms resulted in a significant increase of endometrial cancer cell invasion. The SDF-1-induced increase of endometrial cancer cell invasion was significantly reduced after treatment with KP-10.
Our findings suggest that SDF-1 plays a major role in endometrial cancer invasion. Stromal-derived factor 1-induced invasion can be inhibited by KP-10 treatment.
转移性癌细胞与靶部位之间的串扰对于转移的发展和进展至关重要。破坏这种相互作用将允许设计基于机制的有效和特异性治疗干预措施。我们已经建立了来自不同肿瘤实体的细胞与 MG63 人成骨样细胞的共培养系统来分析肿瘤细胞侵袭。最近，我们已经表明，当与 MG63 细胞共培养时，乳腺癌细胞侵袭显著增加。
使用该模型，我们现在分析了基质衍生因子 1（SDF-1）是否负责人子宫内膜癌细胞的侵袭，以及 kisspeptin-10（KP-10）治疗是否会影响体外 SDF-1 诱导的子宫内膜癌细胞侵袭。
通过评估子宫内膜癌细胞在与 MG63 细胞共培养或在用 SDF-1α、SDF-1β或两种 SDF-1 同工型的组合处理后通过改良 Boyden 室中的人工基底膜的迁移率来量化侵袭。此外，通过在与 MG64 细胞共培养期间阻断 SDF-1 分泌来分析 SDF-1 在子宫内膜癌细胞侵袭中的作用。此外，还分析了 KP-10 处理对 MG63 共培养驱动和 SDF-1 诱导的侵袭的影响。
当与 MG63 细胞共培养时，子宫内膜癌细胞的侵袭明显增加。用 KP-10 处理降低了穿透重建基底膜的能力，并响应细胞刺激而迁移。在 10(-13)至 10(-11)mol/L 的剂量范围内，这种作用是显著的。在共培养期间，MG63 细胞的 SDF-1 蛋白表达显著增加。MG63 共培养诱导的子宫内膜癌细胞侵袭增加可被抗 SDF-1 抗体阻断。用 SDF-1α、SDF-1β或两种同工型的组合处理在单核培养（无 MG63）中的子宫内膜癌细胞导致子宫内膜癌细胞侵袭的显著增加。用 KP-10 处理后，SDF-1 诱导的子宫内膜癌细胞侵袭增加显著降低。
我们的研究结果表明，SDF-1 在子宫内膜癌侵袭中起主要作用。基质衍生因子 1 诱导的侵袭可以通过 KP-10 治疗来抑制。
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