Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital of Würzburg, Würzburg, Germany.
Cells Tissues Organs. 2013;198(5):327-37. doi: 10.1159/000356731. Epub 2013 Dec 20.
Interactions of human mesenchymal stem cells (hMSC) with tumors are controversially discussed since there is evidence for both tumor progression as well as tumor inhibition by hMSC. The objective of the present study is to investigate whether hMSC support cell motility and cytokine secretion in a head and neck squamous cell carcinoma cell line (HLaC 78). A spheroid model was generated in which the ultrastructure of spheroids was analyzed using scanning electron microscopy (SEM). The migration capability was monitored in a monolayer as well as in a spheroid model. The variation in migration and secretion of interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF), as well as the expression of the multidrug resistance gene (MDR-1) was investigated. Finally, the alteration in the cell cycle was analyzed by flow cytometry. SEM showed a tight cell-cell contact with extensive secretion of extracellular matrix. The migration and invasion capability of HLaC 78 was enhanced by hMSC. Cancer cell motility was also increased by hMSC as well as secretion of the cytokines IL-6, IL-8 and VEGF. hMSC did not induce the expression of MDR-1 in HLaC 78, and there was no alteration in the cell cycle of HLaC 78 after cocultivation with hMSC. Our results confirm the important role of hMSC in cancer biology since both an enhancement of cell motility as well as cytokine secretion could be shown. However, based on these findings and those in the current literature, caution must be applied when using hMSC as a carrier for tumor therapy in cancer treatment.
人骨髓间充质干细胞(hMSC)与肿瘤的相互作用存在争议,因为有证据表明 hMSC 既促进肿瘤进展,也抑制肿瘤。本研究的目的是研究 hMSC 是否支持头颈部鳞状细胞癌细胞系(HLaC 78)的细胞迁移和细胞因子分泌。通过扫描电子显微镜(SEM)分析了球体的超微结构,生成了球体模型。在单层和球体模型中监测了迁移能力。研究了迁移和白细胞介素(IL)-6、IL-8 和血管内皮生长因子(VEGF)分泌的变化,以及多药耐药基因(MDR-1)的表达。最后,通过流式细胞术分析了细胞周期的改变。SEM 显示细胞间紧密接触,细胞外基质大量分泌。hMSC 增强了 HLaC 78 的迁移和侵袭能力。hMSC 还增加了癌细胞的迁移能力以及细胞因子 IL-6、IL-8 和 VEGF 的分泌。hMSC 没有诱导 HLaC 78 中 MDR-1 的表达,hMSC 与 HLaC 78 共培养后,HLaC 78 的细胞周期没有改变。我们的结果证实了 hMSC 在癌症生物学中的重要作用,因为可以显示出增强细胞迁移和细胞因子分泌的作用。然而,基于这些发现和当前文献中的发现,在癌症治疗中使用 hMSC 作为肿瘤治疗的载体时必须谨慎。