INSERM UMR 1037 Cancer Research Center of Toulouse (CRCT), University Paul Sabatier Toulouse III, Avenue Hubert Curien, 31100 Toulouse, France.
IUCT-Oncopole, Avenue Hubert Curien, 31100 Toulouse, France.
Cells. 2022 Jul 6;11(14):2128. doi: 10.3390/cells11142128.
Systematic recurrence of glioblastoma (GB) despite surgery and chemo-radiotherapy is due to GB stem cells (GBSC), which are particularly invasive and radioresistant. Therefore, there is a need to identify new factors that might be targeted to decrease GBSC invasive capabilities as well as radioresistance. Patient-derived GBSC were used in this study to demonstrate a higher expression of the glycoprotein M6a (GPM6A) in invasive GBSC compared to non-invasive cells. In 3D invasion assays performed on primary neurospheres of GBSC, we showed that blocking GPM6A expression by siRNA significantly reduced cell invasion. We also demonstrated a high correlation of GPM6A with the oncogenic protein tyrosine phosphatase, PTPRZ1, which regulates GPM6A expression and cell invasion. The results of our study also show that GPM6A and PTPRZ1 are crucial for GBSC sphere formation. Finally, we demonstrated that targeting GPM6A or PTPRZ1 in GBSC increases the radiosensitivity of GBSC. Our results suggest that blocking GPM6A or PTPRZ1 could represent an interesting approach in the treatment of glioblastoma since it would simultaneously target proliferation, invasion, and radioresistance.
尽管手术和放化疗后胶质母细胞瘤（GB）仍会复发，这是由于胶质母细胞瘤干细胞（GBSC）所致，其具有较强的侵袭性和放射抗性。因此，需要确定新的靶点，以降低 GBSC 的侵袭能力和放射抗性。本研究使用患者来源的 GBSC 表明，与非侵袭性细胞相比，侵袭性 GBSC 中糖蛋白 M6a（GPM6A）的表达更高。在 GBSC 原代神经球的 3D 侵袭实验中，我们发现通过 siRNA 阻断 GPM6A 表达可显著降低细胞侵袭。我们还证明了 GPM6A 与癌蛋白酪氨酸磷酸酶 PTPRZ1 高度相关，PTPRZ1 可调节 GPM6A 的表达和细胞侵袭。我们的研究结果还表明，GPM6A 和 PTPRZ1 对于 GBSC 球体形成至关重要。最后，我们证明靶向 GPM6A 或 PTPRZ1 可增加 GBSC 的放射敏感性。我们的研究结果表明，阻断 GPM6A 或 PTPRZ1 可能是治疗胶质母细胞瘤的一种有前途的方法，因为它可同时针对增殖、侵袭和放射抗性。
