Yount Garret, Taft Ryan J, Luu Tri, Rachlin Kenneth, Moore Dan, Zhang Wei
California Pacific Medical Center Research Institute, 475 Brannan Street, Suite 220, San Francisco, CA 94107, USA.
J Neurooncol. 2007 Jan;81(2):113-21. doi: 10.1007/s11060-006-9211-4. Epub 2006 Jul 19.
Diffuse brain invasion contributes to the poor prognosis for patients with gliomas. Analyzing glioma cell migration in vitro, we have demonstrated the spontaneous shedding of anucleate cell fragments that separate from glioma cell bodies and maintain viability from hours to days. Unlike previously described cell fragments that are released from cells as diffusible vectors, glioma cell fragments are independently motile. We used computerized time-lapse microscopy to characterize the formation of these independent motile microplasts (IMMPs) in human cell cultures derived from the most highly invasive glial tumor, glioblastoma. IMMPs were larger than previously described cell fragments, ranging in size from approximately 2% to nearly half of the area of their parent cells. Complex cell-like behaviors-including establishment of polarity, extension of lamellipodia and filopodia, and change in direction of movement-remained intact in IMMPs. The average direction and velocity of the IMMPs were indistinguishable from those of their parent cells. IMMPs formed at a significantly higher rate in glioma cell lines rendered more invasive by overexpression of invasion-related genes than in vector-transfected controls. The correlation with cell invasiveness indicates that IMMP formation may be related to the cell-invasive phenotype. Further investigation will determine whether IMMPs represent a novel addition to the growing list of viable cell fragments with biological relevance.
弥漫性脑浸润导致胶质瘤患者预后不良。通过体外分析胶质瘤细胞迁移，我们发现无核细胞碎片会自发脱落，这些碎片从胶质瘤细胞体分离出来，并在数小时至数天内保持活力。与之前描述的作为可扩散载体从细胞中释放的细胞碎片不同，胶质瘤细胞碎片具有独立运动能力。我们使用计算机延时显微镜来表征这些独立运动微质体（IMMPs）在源自侵袭性最强的胶质肿瘤——胶质母细胞瘤的人类细胞培养物中的形成过程。IMMPs比之前描述的细胞碎片更大，其大小范围约为亲代细胞面积的2%至近一半。复杂的细胞样行为——包括极性的建立、片状伪足和丝状伪足的延伸以及运动方向的改变——在IMMPs中依然完整。IMMPs的平均运动方向和速度与亲代细胞无异。与载体转染的对照相比，在通过过表达侵袭相关基因而更具侵袭性的胶质瘤细胞系中，IMMPs的形成速率显著更高。与细胞侵袭性的相关性表明，IMMPs的形成可能与细胞侵袭表型有关。进一步的研究将确定IMMPs是否代表了与生物学相关的、不断增加的有活力细胞碎片清单中的新成员。
