Merzak A, Koocheckpour S, Pilkington G J
Institute of Psychiatry, Department of Neuropathology, London, United Kingdom.
Cancer Res. 1994 Aug 1;54(15):3988-92.
Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Factors involved in the control of this invasive behavior are poorly documented. Human gliomas have also been found to express CD44 adhesion molecules. Expression of splice variants of CD44 has been correlated to metastasis in nonglial solid tumors. In this study, 8-microns porosity polycarbonate filters incorporated in modified Boyden chambers and coated with the extracellular matrix composite Matrigel were used to investigate the role of CD44 in invasion of eight human glioma cell lines in vitro. Invasion of Matrigel was found to be inhibited to different extents by a CD44 monoclonal antibody. Moreover, this invasion was highly inhibited in two cell lines and completely arrested in five other glioma cell lines by a CD44-specific antisense oligonucleotide which inhibited CD44 expression. In addition, adhesion of glioma cells to fibronectin, laminin, vitronectin, and collagen I was inhibited by the CD44 monoclonal antibody. These results strongly suggest that CD44 is involved in human glioma cell invasion in vitro, probably through its role in cell interactions with extracellular matrix proteins. Interference with glioma invasion, by targeting CD44 expression, may be envisaged in animal models.
人类胶质瘤的特征在于其对正常脑结构的侵袭，而不论其恶性程度如何。关于控制这种侵袭行为的因素，文献记载较少。人们还发现人类胶质瘤表达CD44黏附分子。在非神经胶质实体瘤中，CD44剪接变体的表达与转移相关。在本研究中，将孔径为8微米的聚碳酸酯滤膜置于改良的博伊登小室中，并包被细胞外基质复合物基质胶，用于体外研究CD44在8种人类胶质瘤细胞系侵袭中的作用。发现一种CD44单克隆抗体可不同程度地抑制基质胶侵袭。此外，一种抑制CD44表达的CD44特异性反义寡核苷酸可使两种细胞系的侵袭受到高度抑制，并使另外五种胶质瘤细胞系的侵袭完全停止。此外，CD44单克隆抗体可抑制胶质瘤细胞与纤连蛋白、层粘连蛋白、玻连蛋白和I型胶原的黏附。这些结果强烈表明，CD44参与了体外人类胶质瘤细胞的侵袭，可能是通过其在细胞与细胞外基质蛋白相互作用中的作用。通过靶向CD44表达来干扰胶质瘤侵袭，在动物模型中是可以设想的。
