Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Int J Clin Oncol. 2020 Jun;25(6):1055-1066. doi: 10.1007/s10147-020-01636-7. Epub 2020 Feb 27.
Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM).
ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.
ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2.
Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.
在哺乳动物组织中，细丝蛋白 A 是细丝蛋白中表达最广泛的同工型。它可以被钙蛋白酶水解，产生一个 90kDa 的羧基末端片段（ABP90）。钙蛋白酶抑制剂 calpeptin 是钙蛋白酶的化学抑制剂，可以抑制这种作用。已经表明，ABP90 作为一种转录因子，参与调节细胞信号转导。然而，在多形性胶质母细胞瘤（GBM）中，ABP90 的意义及其潜在机制的临床特征尚未得到很好的研究。
通过 Western blot 检测 36 名胶质瘤患者的 ABP90 蛋白。使用人 GBM 细胞系 U87 和 A172 来阐明 ABP90 的精确作用。CCK-8 测定法用于分析细胞活力。Transwell 侵袭实验和划痕愈合实验用于分析迁移和侵袭。Western blot 用于分析基质金属蛋白酶 2/金属蛋白酶组织抑制剂 2（MMP2/TIMP2）蛋白的表达。
GBM 组织中 ABP90 蛋白表达较低。ABP90 蛋白低表达的患者 OS 时间更短（p=0.046）。在用钙蛋白酶处理后，ABP90 的表达上调，导致细胞活力下降，增强替莫唑胺的疗效，并抑制细胞侵袭。Calpeptin 可以抑制这种作用。其机制可能涉及 MMP2/TIMP2 的平衡。
我们目前的数据表明，ABP90 表达是一个重要的预后因素，可能在 GBM 的细胞活力、化疗敏感性和侵袭中发挥重要作用。
