多形性成膠質(zhì)細胞瘤,，圖片來自Keith A. Johnson ([email protected])和J. Alex Becker ([email protected])
腦癌很難治療：它不僅頑強抵抗大多數(shù)化療,，而且足夠靈活地從放療或手術(shù)位點遷移到他處導(dǎo)致癌癥再生,。如今美國科羅拉多大學(xué)癌癥中心研究人員開展的這項新研究表明如何阻止這兩者發(fā)生,。
特別的是，癌細胞給它們自己發(fā)送存活、生長、增殖和遷移的信號,。兩年前，科羅拉多大學(xué)癌癥中心研究人員表明關(guān)閉一組信號使得腦癌細胞不那么頑強,，它使得這些之前抵抗治療的細胞對化療敏感,。但是第二個問題即遷移問題，潛在性地一直存在,。
科羅拉多大學(xué)癌癥中心研究員Amy Keating醫(yī)學(xué)博士,，也是這項發(fā)表在Oncogene期刊上新研究的通信作者，他說,，“我早就認為這是治療這種癌癥的好方法,，但是需要審核一下我們不會導(dǎo)致其他問題。我們想知道關(guān)閉TAM信號家族 (TAM family signaling)是否會使得腦癌細胞遷移到一個新位點---在那里它們可能產(chǎn)生新的問題,。”
因此,，Keating和同事們就深入研究這種TAM信號家族來探索它的成員如何影響增殖和遷移。當(dāng)他們抑制通過其他家族成員Axl抑制信號傳導(dǎo)時,，很少發(fā)生變化(確實這是好消息：至少關(guān)閉這種信號傳導(dǎo)途徑并不促進癌細胞遷移)。
但是當(dāng)Keating和同事們通過Mer途徑關(guān)閉信號傳導(dǎo)時,，它剛好合適,，這些受影響的癌細胞不僅對化療更敏感，而且也不能逃離到大腦中更安全的區(qū)域,。
當(dāng)前在美國,，多形性成膠質(zhì)細胞瘤(glioblastoma multiforme)每年影響45000個人，他們當(dāng)中大多數(shù)人在確診后不能存活14個月,。
Keating說,，“這代表著一種新靶向治療，提供一種潛在性的之前沒有人嘗試過的新方法,。”
在細胞系上發(fā)現(xiàn)的這些極其有希望的結(jié)果之后,，Keating和同事們當(dāng)前正在小鼠中測試這項技術(shù)，在此之后,，他們希望很快轉(zhuǎn)移到人類臨床試驗中,。(生物谷：towersimper編譯)
doi:10.1038/onc.2011.588
PMC:
PMID:
Mer receptor tyrosine kinase inhibition impedes glioblastoma multiforme migration and alters cellular morphology
A E J Rogers, J P Le, S Sather, B M Pernu, D K Graham, A M Pierce and A K Keating
Glioblastoma multiforme (GBM) is an aggressive brain tumor, fatal within 1 year from diagnosis in most patients despite intensive multimodality therapy. The migratory and microscopically invasive nature of GBM as well as its resistance to chemotherapy renders conventional therapies inadequate in its treatment. Although Mer receptor tyrosine kinase (RTK) inhibition has been shown to decrease the long-term survival and improve the chemosensitivity of GBM in vitro, its role in malignant cellular migration has not been previously evaluated. In this study, we report for the first time a role for Mer RTK in brain tumor migration and show that Mer inhibition profoundly impedes GBM migration and alters cellular morphology. Our data demonstrate that Mer RTK inhibition results in altered signaling through focal adhesion kinase (FAK) and RhoA GTPase and a transformation of cytoskeletal organization, suggesting both molecular and structural mechanisms for the abrogation of migration. We also describe a novel and translational method of Mer RTK inhibition using a newly developed monoclonal antibody, providing proof of principle for future evaluation of Mer-targeted translational therapies in the treatment of GBM. Previous findings implicating Mer signaling in glioblastoma survival and chemotherapy resistance coupled with our discovery of the role of Mer RTK in GBM cellular migration support the development of novel Mer-targeted therapies for this devastating disease.
