Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats.
Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats.
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
Catherine L. Nutt;C. Zerillo;G. Kelly;S. Hockfield
中科院分区：
文献类型：
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作者：
Catherine L. Nutt;C. Zerillo;G. Kelly;S. Hockfield
胶质瘤是最常见的原发性颅内肿瘤。一种与神经胶质肿瘤生物学有关的细胞外基质成分是脑富集透明质酸结合(BEHAB)/brevican。在这项研究中，用含有全长BEHAB/brevican cDNA的载体转染CNS-1大鼠胶质瘤细胞系，其中5‘插入编码NH(2)末端BEHAB/brevican切割产物，或3’插入编码cooh末端切割产物。作为对照，用绿色荧光蛋白转染CNS-1细胞。经BEHAB/brevican转染的CNS-1细胞颅内移植大鼠的存活时间明显短于cns -绿色荧光蛋白颅内移植大鼠（P < 0.001）。组织学检查显示，尽管BEHAB/brevican肿瘤的生长时间仅为对照肿瘤的大约三分之二，但转染了BEHAB/brevican的肿瘤与对照肿瘤的侵袭性相同，甚至更强。这些数据表明，BEHAB/brevican的上调和蛋白水解裂解可显著增加胶质肿瘤的侵袭性。因此，研究抑制BEHAB/brevican切割在这些细胞中的作用，并确定抑制BEHAB/brevican切割在胶质瘤中的治疗潜力将具有重要意义。
Gliomas are the most common primary intracranial tumors. One extracellular matrix component that has been implicated in glial tumor biology is brain enriched hyaluronan binding (BEHAB)/brevican. In this study, the CNS-1 rat glioma cell line was transfected with a vector containing either a full-length BEHAB/brevican cDNA, a 5' insert encoding the NH(2)-terminal BEHAB/brevican cleavage product, or a 3' insert encoding the COOH-terminal cleavage product. As a control, CNS-1 cells were transfected with green fluorescent protein. Rats with intracranial grafts of BEHAB/brevican-transfected CNS-1 cells displayed significantly shorter survival times than did rats with CNS-green fluorescent protein intracranial grafts (P < 0.001). Histological examination showed that the BEHAB/brevican-transfected tumors were just as, if not more, aggressive than control tumors, even though the BEHAB/brevican tumors had been growing for only approximately two-thirds the time as long as control tumors. These data suggest that up-regulation and proteolytic cleavage of BEHAB/brevican increase significantly the aggressiveness of glial tumors. It will be important to investigate the effect of inhibiting cleavage of BEHAB/brevican in these cells and to determine the therapeutic potential of inhibiting BEHAB/brevican cleavage in gliomas.