Motaln Helena, Turnsek Tamara Lah
National Institute of Biology, Vecna pot 111, 1000 Ljubljana, Slovenia.
Protein Pept Lett. 2015;22(4):322-31. doi: 10.2174/0929866522666150131123808.
Numerous small molecules including cytokines primarily associated with immune response have been shown to play a role in normal mesenchymal stem cells (MSC) and tumour cells' communication. One characteristic that distinguishes MSC from fibroblast and other cells of mesenchymal origin is their pro-tumour migratory behaviour. Recognizing the cytokines as key players of the MSC/tumour cell cross-talk and understanding their intracellular signalling, should lead to a development of more efficient anti-tumour therapies. Those are urgently needed for improving the treatment of patients with glioblastoma multiformae (GBM) that are suffering from most aggressive and incurable type of brain tumours. So far, the "cytokine signalling interference" approach, employing genetically modified MSCs and GBM cells in animal xenograft models pointed to the mechanisms underlying tumour - directed migration and immunomodulatory role of MSCs. There, MSC's effects on tumour growth were shown to vary substantially, and to depend on the type of the cells and the animal model used. This review is focusing on the cytokines produced by MSCs and their involvement in proliferation, migration, angiogenesis, apoptosis and immune cell infiltration. Recently, targeted therapies have emerged as a promising modality for GBM treatment. New approaches, combining these with MSCs as cellular vectors for modulating cytokines and cytokine receptors' signalling in GBM may thus prove more efficient at inhibiting glioma progression.
许多小分子,包括主要与免疫反应相关的细胞因子,已被证明在正常间充质干细胞(MSC)与肿瘤细胞的通讯中发挥作用。MSC与成纤维细胞及其他间充质来源细胞的一个区别特征是它们的促肿瘤迁移行为。认识到细胞因子是MSC/肿瘤细胞相互作用的关键参与者,并了解它们的细胞内信号传导,应该会带来更有效的抗肿瘤治疗方法的发展。对于改善患有最具侵袭性和无法治愈的脑肿瘤——多形性胶质母细胞瘤(GBM)的患者的治疗而言,这些方法是迫切需要的。到目前为止,在动物异种移植模型中采用基因改造的MSC和GBM细胞的“细胞因子信号干扰”方法,揭示了肿瘤定向迁移和MSC免疫调节作用的潜在机制。在那里,MSC对肿瘤生长的影响显示出很大差异,并取决于所使用的细胞类型和动物模型。本综述聚焦于MSC产生的细胞因子及其在增殖、迁移、血管生成、凋亡和免疫细胞浸润中的作用。最近,靶向治疗已成为GBM治疗的一种有前景的方式。因此,将这些方法与MSC结合作为调节GBM中细胞因子和细胞因子受体信号传导的细胞载体的新方法,可能在抑制胶质瘤进展方面更有效。