Radotra B, McCormick D
Neuro-Oncology Laboratory, Queen's University of Belfast, United Kingdom.
Anticancer Res. 1997 Mar-Apr;17(2A):945-9.
Local tumour-cell invasiveness, which is a major morphological feature of astrocytomas, involves interactions between tumour cell and extracellular matrix (ECM) including adhesion, proteolysis, and migration of tumour cells through the locally modified microenvironment. These interactions are mediated by cell/cell and cell/substrate adhesion molecules. We have earlier demonstrated that the adhesion molecule CD44 is expressed on gliomas and plays a role in adhesive interactions between glioma cells and a wide range of ECM components. In the present in vitro study we have further investigated the possible role of CD44 in subsequent stages of cell/ECM interactions-spreading and migration, using the GCCM anaplastic astrocytoma cell line. We have demonstrated that cell spreading is more effective on fibronectin (FN) than hyaluronan (HA) with a mean cell perimeter of 185 microns when cells are grown on FN as compared to 66 microns on HA. Antibody blockade experiments indicated that CD44 is not involved in cell spreading on either substrate. In the in vitro migration assay the tumour cells displayed a 2.5 fold greater migration rate through HA-coated as compared to FN-coated polycarbonate membranes. Blocking of CD44 by specific monoclonal antibody resulted in an inhibition of migration by 56% on HA providing evidence that CD44 plays a role in migration of astrocytoma cells in vitro.
局部肿瘤细胞侵袭是星形细胞瘤的一个主要形态学特征,涉及肿瘤细胞与细胞外基质(ECM)之间的相互作用,包括肿瘤细胞的黏附、蛋白水解以及通过局部改变的微环境进行迁移。这些相互作用由细胞/细胞和细胞/底物黏附分子介导。我们之前已经证明黏附分子CD44在胶质瘤上表达,并在胶质瘤细胞与多种ECM成分之间的黏附相互作用中发挥作用。在本体外研究中,我们使用GCCM间变性星形细胞瘤细胞系,进一步研究了CD44在细胞/ECM相互作用的后续阶段——铺展和迁移中的可能作用。我们已经证明,细胞在纤连蛋白(FN)上的铺展比在透明质酸(HA)上更有效,当细胞在FN上生长时,平均细胞周长为185微米,而在HA上为66微米。抗体阻断实验表明,CD44不参与细胞在任何一种底物上的铺展。在体外迁移试验中,与FN包被的聚碳酸酯膜相比,肿瘤细胞通过HA包被的膜的迁移率高2.5倍。用特异性单克隆抗体阻断CD44导致在HA上的迁移受到56%的抑制,这证明CD44在体外星形细胞瘤细胞的迁移中发挥作用。