近日，弗里德里希Miescher生物医学研究所科学家完成的一项最近研究发现了恶性脑肿瘤治疗的新靶点。科学家发现人类脑肿瘤中高表达Mer受体酪氨酸激酶（MerTK），但正常成人脑组织中不表达。MerTK不仅能增加脑源性肿瘤细胞的侵袭能力，同时在化疗药物治疗时，也能促进了肿瘤细胞的生存。相反减少MerTK的表达后，肿瘤细胞的侵袭能力减弱。
胶质母细胞瘤是星形细胞肿瘤中恶性程度最高的胶质瘤 属WHO Ⅳ级。肿瘤位于皮质下， 成浸润性生长， 常侵犯几个脑叶，并侵犯深部结构，还可经胼胝体波及对侧大脑半球。发生部位以额叶最多见，其他依次为颞叶、顶叶，少数可见于枕叶/丘脑和基底节等。
弗里德里希Miescher生物医学研究所Brian Hemmings科学家与临床医生和病理学家一起合作发现在恶性胶质瘤中MerTK高表达，但正常脑组织中不表达。为了研究其中基本机制，研究人员创建GBM衍生细胞株发现MerTK没有在这些细胞中表达，进一步的实验显示MerTK通过调节肌动球蛋白的收缩驱动GBM细胞的侵袭，从而使得侵入的肿瘤细胞进入周围的脑组织。最后，科学家们发现，MerTK蛋白表达诱导DNA损伤，保护脑胶质瘤细胞免受细胞毒性的伤害。最后研究结果表明MerTK是保护胶质瘤细胞存活和放疗后的增强其入侵能力的部分驱动因素。
放射治疗是最常用的恶性脑胶质瘤的治疗方法，它能显著延长患者寿命，尽管许多胶质瘤患者出现初步治疗应答，但都会出现复发现象。90％的GBM肿瘤MerTK过度表达，因此研究人员认为MerTK或许可作为一个潜在的治疗恶性脑胶质瘤的新靶标。（生物谷：Bioon.com）
doi:10.1038/onc.2012.104
PMC:
PMID:
Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme
Y Wang, G Moncayo, P Morin Jr, G Xue, M Grzmil, M M Lino, V Clément-Schatlo, S Frank, A Merlo and B A Hemmings
The infiltration of glioma cells into adjacent tissue is one of the major obstacles in the therapeutic management of malignant brain tumours, in most cases precluding complete surgical resection. Consequently, malignant glioma patients almost invariably experience tumour recurrences. Within the brain, glioma cells migrate rapidly either amoeboidly or mesenchymally to invade surrounding structures, in dependence on the extracellular environment. In addition, radiotherapy, frequently applied as adjuvant therapeutic modality, may enhance tumour cell mobility. Here, we show that the receptor tyrosine kinase Mer (MerTK) is overexpressed in glioblastoma multiforme (GBM) and that this is accompanied with increased invasive potential. MerTK expression is maintained in primary GBM-derived tumour spheres under stem cell culture conditions but diminishes significantly in serum-containing cultures with concomitant downregulation of Nestin and Sox2. Depletion of MerTK disrupts the rounded morphology of glioma cells and decreases their invasive capacity. Furthermore, the expression and phosphorylation of myosin light chain 2 are strongly associated with MerTK activity, indicating that the effect of MerTK on glioma cell invasion is mediated by actomyosin contractility. Finally, DNA damage robustly triggers the upregulation and phosphorylation of MerTK, which protects cells from apoptosis. This effect is strongly impaired upon MerTK depletion or overexpression of an inactive MerTK mutant. Collectively, our data suggests that MerTK is a novel therapeutic target in the treatment of the malignant gliomas.
