多形性成胶质细胞瘤，图片来自Keith A. Johnson (keith@bwh.harvard.edu)和J. Alex Becker (jabecker@mit.edu)
脑癌很难治疗：它不仅顽强抵抗大多数化疗，而且足够灵活地从放疗或手术位点迁移到他处导致癌症再生。如今美国科罗拉多大学癌症中心研究人员开展的这项新研究表明如何阻止这两者发生。
特别的是，癌细胞给它们自己发送存活、生长、增殖和迁移的信号。两年前，科罗拉多大学癌症中心研究人员表明关闭一组信号使得脑癌细胞不那么顽强，它使得这些之前抵抗治疗的细胞对化疗敏感。但是第二个问题即迁移问题，潜在性地一直存在。
科罗拉多大学癌症中心研究员Amy Keating医学博士，也是这项发表在Oncogene期刊上新研究的通信作者，他说，“我早就认为这是治疗这种癌症的好方法，但是需要审核一下我们不会导致其他问题。我们想知道关闭TAM信号家族 (TAM family signaling)是否会使得脑癌细胞迁移到一个新位点---在那里它们可能产生新的问题。”
因此，Keating和同事们就深入研究这种TAM信号家族来探索它的成员如何影响增殖和迁移。当他们抑制通过其他家族成员Axl抑制信号传导时，很少发生变化(确实这是好消息：至少关闭这种信号传导途径并不促进癌细胞迁移)。
但是当Keating和同事们通过Mer途径关闭信号传导时，它刚好合适，这些受影响的癌细胞不仅对化疗更敏感，而且也不能逃离到大脑中更安全的区域。
当前在美国，多形性成胶质细胞瘤(glioblastoma multiforme)每年影响45000个人，他们当中大多数人在确诊后不能存活14个月。
Keating说，“这代表着一种新靶向治疗，提供一种潜在性的之前没有人尝试过的新方法。”
在细胞系上发现的这些极其有希望的结果之后，Keating和同事们当前正在小鼠中测试这项技术，在此之后，他们希望很快转移到人类临床试验中。(生物谷：towersimper编译)
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.
