近日,，弗里德里希Miescher生物醫(yī)學(xué)研究所科學(xué)家完成的一項(xiàng)最近研究發(fā)現(xiàn)了惡性腦腫瘤治療的新靶點(diǎn)?？茖W(xué)家發(fā)現(xiàn)人類腦腫瘤中高表達(dá)Mer受體酪氨酸激酶（MerTK）,，但正常成人腦組織中不表達(dá)。MerTK不僅能增加腦源性腫瘤細(xì)胞的侵襲能力,，同時(shí)在化療藥物治療時(shí),，也能促進(jìn)了腫瘤細(xì)胞的生存,。相反減少M(fèi)erTK的表達(dá)后,，腫瘤細(xì)胞的侵襲能力減弱。
膠質(zhì)母細(xì)胞瘤是星形細(xì)胞腫瘤中惡性程度最高的膠質(zhì)瘤 屬WHO Ⅳ級(jí),。腫瘤位于皮質(zhì)下,， 成浸潤性生長,， 常侵犯幾個(gè)腦葉，并侵犯深部結(jié)構(gòu),，還可經(jīng)胼胝體波及對(duì)側(cè)大腦半球,。發(fā)生部位以額葉最多見，其他依次為顳葉,、頂葉,，少數(shù)可見于枕葉/丘腦和基底節(jié)等。
弗里德里希Miescher生物醫(yī)學(xué)研究所Brian Hemmings科學(xué)家與臨床醫(yī)生和病理學(xué)家一起合作發(fā)現(xiàn)在惡性膠質(zhì)瘤中MerTK高表達(dá),，但正常腦組織中不表達(dá),。為了研究其中基本機(jī)制，研究人員創(chuàng)建GBM衍生細(xì)胞株發(fā)現(xiàn)MerTK沒有在這些細(xì)胞中表達(dá)，進(jìn)一步的實(shí)驗(yàn)顯示MerTK通過調(diào)節(jié)肌動(dòng)球蛋白的收縮驅(qū)動(dòng)GBM細(xì)胞的侵襲,，從而使得侵入的腫瘤細(xì)胞進(jìn)入周圍的腦組織,。最后，科學(xué)家們發(fā)現(xiàn),，MerTK蛋白表達(dá)誘導(dǎo)DNA損傷,，保護(hù)腦膠質(zhì)瘤細(xì)胞免受細(xì)胞毒性的傷害。最后研究結(jié)果表明MerTK是保護(hù)膠質(zhì)瘤細(xì)胞存活和放療后的增強(qiáng)其入侵能力的部分驅(qū)動(dòng)因素,。
放射治療是最常用的惡性腦膠質(zhì)瘤的治療方法,，它能顯著延長患者壽命，盡管許多膠質(zhì)瘤患者出現(xiàn)初步治療應(yīng)答,，但都會(huì)出現(xiàn)復(fù)發(fā)現(xiàn)象,。90％的GBM腫瘤MerTK過度表達(dá)，因此研究人員認(rèn)為MerTK或許可作為一個(gè)潛在的治療惡性腦膠質(zhì)瘤的新靶標(biāo),。（生物谷：Bioon.com）
doi:10.1038/onc.2012.104
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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.
