Laboratoire Neurobiologie & Transgenese, Centre Hospitalier Universitaire, Angers, France.
Mol Ther. 2012 Jul;20(7):1367-77. doi: 10.1038/mt.2012.45. Epub 2012 Apr 10.
Despite aggressive treatment regimes, glioma remains a largely fatal disease. Current treatment limitations are attributed to the precarious locations within the brain where such tumors grow, their highly infiltrative nature precluding complete resection and lack of specificity among agents capable of attenuating their growth. Here, we show that in vitro, glioma cells of diverse origins internalize a peptide encompassing a tubulin-binding site (TBS) on the neurofilament light protein. The internalized peptide disrupts the microtubule network, inhibits migration and proliferation, and leads to apoptosis. Using an intracerebral transplant model, we show that most, if not all, of these responses to peptide exposure also occur in vivo. Notably, a single intratumor injection significantly attenuates tumor growth, while neither peptide uptake nor downstream consequences are observed elsewhere in the host nervous system. Such preferential uptake suggests that the peptide may have potential as a primary or supplementary glioblastoma treatment modality by exploiting its autonomous microtubule-disrupting activity or engaging its capacity to selectively target glioma cells with other cell-disrupting cargos.
尽管采取了积极的治疗方案，神经胶质瘤仍然是一种主要的致命疾病。目前的治疗局限性归因于这些肿瘤生长的大脑内部位置不稳定，其高度浸润性性质排除了完全切除的可能性，以及能够减缓其生长的药物缺乏特异性。在这里，我们表明，在体外，源自不同来源的神经胶质瘤细胞内化了包含神经丝轻蛋白上的微管结合位点 (TBS) 的肽。内化的肽破坏微管网络，抑制迁移和增殖，并导致细胞凋亡。使用脑内移植模型，我们表明，肽暴露后的这些反应大多数（如果不是全部）也在体内发生。值得注意的是，单次肿瘤内注射可显著抑制肿瘤生长，而在宿主神经系统的其他部位既没有观察到肽摄取也没有观察到下游后果。这种优先摄取表明该肽可能具有作为胶质母细胞瘤主要或辅助治疗方式的潜力，通过利用其自主的微管破坏活性或利用其选择性靶向带有其他细胞破坏有效负载的神经胶质瘤细胞的能力。
