Hoshimaru Takumi, Nonoguchi Naosuke, Kosaka Takuya, Furuse Motomasa, Kawabata Shinji, Yagi Ryokichi, Kurisu Yoshitaka, Kashiwagi Hideki, Kameda Masahiro, Takami Toshihiro, Kataoka-Sasaki Yuko, Sasaki Masanori, Honmou Osamu, Hiramatsu Ryo, Wanibuchi Masahiko
Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Department of Pathology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Brain Sci. 2023 Oct 19;13(10):1477. doi: 10.3390/brainsci13101477.
Malignant glioma is a highly invasive tumor, and elucidating the glioma invasion mechanism is essential for developing novel therapies. We aimed to highlight actin alpha 2, smooth muscle (ACTA2) as potential biomarkers of brain invasion and distant recurrence in malignant gliomas. Using the human malignant glioma cell line, U251MG, we generated ACTA2 knockdown (KD) cells treated with small interfering RNA, and the cell motility and proliferation of the ACTA2 KD group were analyzed. Furthermore, tumor samples from 12 glioma patients who underwent reoperation at the time of tumor recurrence were utilized to measure ACTA2 expression in the tumors before and after recurrence. Thereafter, we examined how ACTA2 expression correlates with the time to tumor recurrence and the mode of recurrence. The results showed that the ACTA2 KD group demonstrated a decline in the mean motion distance and proliferative capacity compared to the control group. In the clinical glioma samples, ACTA2 expression was remarkably increased in recurrent samples compared to the primary samples from the same patients, and the higher the change in ACTCA2 expression from the start to relapse, the shorter the progression-free survival. In conclusion, ACTA2 may be involved in distant recurrence in clinical gliomas.
恶性胶质瘤是一种具有高度侵袭性的肿瘤,阐明胶质瘤的侵袭机制对于开发新疗法至关重要。我们旨在强调平滑肌肌动蛋白α2(ACTA2)作为恶性胶质瘤脑侵袭和远处复发的潜在生物标志物。使用人恶性胶质瘤细胞系U251MG,我们生成了用小干扰RNA处理的ACTA2敲低(KD)细胞,并分析了ACTA2 KD组的细胞运动性和增殖情况。此外,利用12例肿瘤复发时接受再次手术的胶质瘤患者的肿瘤样本,测量复发前后肿瘤中ACTA2的表达。此后,我们研究了ACTA2表达与肿瘤复发时间和复发模式之间的关系。结果显示,与对照组相比,ACTA2 KD组的平均运动距离和增殖能力有所下降。在临床胶质瘤样本中,与同一患者的原发样本相比,复发样本中ACTA2表达显著增加,并且从开始到复发时ACTC2表达的变化越大,无进展生存期越短。总之,ACTA2可能参与临床胶质瘤的远处复发。