Evidence for a secreted chemorepellent that directs glioma cell invasion.
Evidence for a secreted chemorepellent that directs glioma cell invasion.
复制标题
分泌的化学驱避剂可引导神经胶质瘤细胞侵袭的证据。
DOI：
--
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
R. Del Maestro
中科院分区：
文献类型：
--
作者：
T. Werbowetski;R. Bjerkvig;R. Del Maestro
在神经发育过程中，分泌的趋化性线索引导神经元和神经胶质细胞前体的迁移。尚不清楚趋化性是否有助于指导神经胶质瘤细胞侵入脑组织。已经开发了一个模型系统，该系统允许使用包埋在胶原凝胶中的胶质瘤球体来量化侵入行为。在这里，我们提供的证据表明，胶质瘤球体分泌的化学排斥因子（S），指导细胞远离球体，进入胶原基质。总侵袭、细胞数量和植入距离之间的关系表明，胶质瘤细胞对在48 h时充分建立的化学排斥性线索的梯度有反应。C6星形细胞瘤细胞通常以垂直于球体边缘的角度侵入胶原。相反，相邻的球状体会导致细胞偏离其正常轨迹，并减缓其侵袭速度。星形细胞瘤细胞被邻近的胶质瘤球体排斥，但迅速浸润星形胶质细胞聚集体，表明星形胶质细胞不表达排斥性信号。在球状体条件培养基中均匀浓度的排斥因子压倒内源性梯度，并使胶质瘤细胞不太能够表现出这种趋化性反应。在细胞迁移测定中，球状体条件培养基的浓度梯度也证明了化学排斥性因子的向性效应。我们的研究结果表明胶质瘤球状体产生一种分泌的可扩散的线索，促进胶质瘤细胞的侵袭。这种因子的鉴定可能会推进旨在限制肿瘤细胞侵袭的当前疗法。
Secreted chemotropic cues guide the migration of neuronal and glial cell precursors during neural development. It is not known if chemotropism contributes to directing the invasion of brain tissue by glioma cells. A model system has been developed that allows quantification of invasive behavior using gliomas spheroids embedded in collagen gels. Here we provide evidence that glioma spheroids secrete a chemorepellent factor(s) that directs cells away from the spheroid and into the collagen matrix. The relationship between total invasion, cell number, and implantation distance suggests that glioma cells respond to a gradient of the chemorepellent cue(s) that is well established at 48 h. C6 astrocytoma cells normally invade the collagen at an angle perpendicular to the spheroid edge. In contrast, an adjacent spheroid causes cells to turn away from their normal trajectory and slow their rate of invasion. Astrocytoma cells are repelled by an adjacent glioma spheroid but rapidly infiltrate astrocyte aggregates, indicating that astrocytes do not express the repellent cue. Uniform concentrations of repellent factor(s) in spheroid conditioned medium overwhelm endogenous gradients and render glioma cells less able to exhibit this chemotropic response. Concentration gradients of spheroid conditioned medium in cell migration assays also demonstrate the chemorepellent cue(s)'s tropic effect. Our findings indicate that glioma spheroids produce a secreted diffusible cue(s) that promotes glioma cell invasion. Identification of this factor(s) may advance current therapies that aim to limit tumor cell invasion.
登录
查看更多内容
体外连合轴突的方向响应底板衍生的化学引诱剂。
DOI：
10.1242/dev.110.1.19
发表时间：
1990
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Placzek,M;Tessier-Lavigne,M;Jessell,T;Dodd,J
通讯作者：
Dodd,J
DOI：
10.1073/pnas.97.23.12846
发表时间：
2000-11-07
影响因子：
11.1
作者：
Aboody, KS;Brown, A;Snyder, EY
通讯作者：
Snyder, EY
C6 神经胶质瘤-星形细胞瘤细胞和胎儿星形胶质细胞迁移到人工基底膜：神经肿瘤但不是胎儿星形胶质细胞的允许基质。
影响因子：
4.8
作者：
Bernstein,JJ;LawsJr,ER;Levine,KV;Wood,LR;Tadvalkar,G;Goldberg,WJ
通讯作者：
Goldberg,WJ
影响因子：
4.1
作者：
CHICOINE, MR;SILBERGELD, DL
通讯作者：
SILBERGELD, DL