Zhang Junwen, Fang Sheng, Song Wenjie, Zhang Bo, Fan Wenhua, Jin Guishan, Liu Fusheng
Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Laboratory of Biomedical Materials, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100070, People's Republic of China.
Onco Targets Ther. 2020 Sep 11;13:9085-9099. doi: 10.2147/OTT.S265322. eCollection 2020.
Gliomas are common intracranial tumors, of which 70% are malignant gliomas. Glioblastoma multiforme (GBM) is the most aggressive tumor, and patients with GBM have a median survival time of only 9-12 months; extracranial recurrence of GBM is very rare. A therapeutic strategy for this kind of recurrent tumor is lacking.
We present a case of a patient with extracranial recurrence of subscalp GBM. The subscalp tumor was resected and xenotransplanted into BALB/C nude mice. Then, glioma cells were isolated from the xenograft models and passaged in vitro. HE staining, immunohistochemistry, CCK-8 assays, karyotypic analysis, short tandem repeat STR analysis and flow cytometry were used to analyze the biological characteristics and malignant phenotype of these established cells. The cells and xenografts were then used as preclinical models to evaluate the antitumor efficacy of oncolytic herpes simplex virus 1 (oHSV-1).
The isolated cells, which were named BT-01, were positive for Nestin and GFAP. The main characteristics of BT-01 cells were that they harbored glioblastoma stem-like cells (GSCs) and that they possessed highly aggressive migration capacities compared with the existing cell lines U87-MG and U251-MG. Moreover, BT-01 cells tolerated the chemotherapeutic drug temozolomide. Our study showed that oHSV-1 could replicate in and repress the growth of BT-01 cells and significantly inhibit tumor growth in xenograft models.
Taken together, our results showed that a new recurrent glioblastoma cell line was established, which can be useful for research on recurrent glioblastoma. We provided a reliable preclinical model to evaluate the antitumor efficacy of oHSV-1 in vivo and a promising therapy for recurrent GBM.
胶质瘤是常见的颅内肿瘤，其中70%为恶性胶质瘤。多形性胶质母细胞瘤（GBM）是最具侵袭性的肿瘤，GBM患者的中位生存时间仅为9 - 12个月；GBM的颅外复发非常罕见。目前缺乏针对这类复发性肿瘤的治疗策略。
我们报告一例头皮下GBM颅外复发的患者。切除头皮下肿瘤并将其异种移植到BALB/C裸鼠体内。然后，从异种移植模型中分离胶质瘤细胞并进行体外传代培养。采用苏木精-伊红（HE）染色、免疫组织化学、CCK-8检测、核型分析、短串联重复序列（STR）分析和流式细胞术分析这些已建立细胞的生物学特性和恶性表型。然后将这些细胞和异种移植瘤用作临床前模型，以评估溶瘤性单纯疱疹病毒1（oHSV-1）的抗肿瘤疗效。
分离得到的细胞命名为BT-01，其巢蛋白（Nestin）和胶质纤维酸性蛋白（GFAP）呈阳性。BT-01细胞的主要特征是它们含有胶质母细胞瘤干细胞样细胞（GSCs），并且与现有的细胞系U87-MG和U251-MG相比，具有高度侵袭性的迁移能力。此外，BT-01细胞对化疗药物替莫唑胺具有耐受性。我们的研究表明，oHSV-1可以在BT-01细胞中复制并抑制其生长，并显著抑制异种移植模型中的肿瘤生长。
综上所述，我们的结果表明建立了一种新的复发性胶质母细胞瘤细胞系，这对于复发性胶质母细胞瘤的研究可能有用。我们提供了一个可靠的临床前模型来评估oHSV-Ⅰ在体内的抗肿瘤疗效，并为复发性GBM提供了一种有前景的治疗方法。
