Preclinical Models and New Therapeutic Agents Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
Institute of Molecular Biology and Pathology, National Research Council, Via Degli Apuli 4, 00185, Rome, Italy.
Cell Death Dis. 2017 Dec 13;8(12):3216. doi: 10.1038/s41419-017-0055-y.
By using human melanoma and glioblastoma cell lines and their derivative BCL-X overexpressing clones, we investigated the role of BCL-X in aggressive features of these two tumor histotypes. We found that in both models, BCL-X overexpression increased in vitro cell migration and invasion and facilitated tumor cells to form de novo vasculogenic structures. Furthermore, BCL-X overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-X plays essential roles in the maintenance of cancer stem cell phenotype. BCL-X expression reduction by siRNA, the exposure to a BCL-X-specific inhibitor and the use of a panel of human melanoma cell lines corroborated the evidence that BCL-X regulates tumor progression-associated properties. Finally, the vascular markers and the vasculogenic mimicry were up-regulated in the BCL-X overexpressing xenografts derived from both tumor histotypes. In conclusion, our work brings further support to the understanding of the malignant actions of BCL-X and, in particular, to the concept that BCL-X promotes stemness and contributes to the aggressiveness of both melanoma and glioblastoma.
通过使用人黑色素瘤和神经胶质瘤细胞系及其衍生的 BCL-X 过表达克隆，我们研究了 BCL-X 在这两种肿瘤组织类型中侵袭性特征的作用。我们发现，在这两种模型中，BCL-X 的过表达均增加了体外细胞迁移和侵袭，并促进肿瘤细胞形成新的血管生成结构。此外，BCL-X 过表达细胞表现出更高的肿瘤球体形成能力，并表达更高水平的一些干细胞标记物，支持 BCL-X 在维持癌症干细胞表型方面发挥重要作用的概念。BCL-X 的 siRNA 表达减少、BCL-X 特异性抑制剂的暴露以及一系列人黑色素瘤细胞系的使用证实了 BCL-X 调节肿瘤进展相关特性的证据。最后，血管标记物和血管生成拟态在上皮来源的两种肿瘤组织类型的 BCL-X 过表达异种移植物中均上调。总之，我们的工作进一步支持了对 BCL-X 的恶性作用的理解，特别是 BCL-X 促进干性和促进黑色素瘤和神经胶质瘤的侵袭性的概念。
