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MODULATION OF CELL BEHAVIORS BY PROTEOGLYCANS WITH ANTI-CELL-SUBSTRATE ADHESION ACTIVITY-STUDIES ON INVOLVING MOLECULES AND THE MECHANISM

具有抗细胞基质粘附活性的蛋白多糖对细胞行为的调节作用-涉及分子及机制的研究

基本信息

批准号：
04454595
负责人：
KIMATA Koji
金额：
$ 3.33万
依托单位：
INSTITUTION FOR MOLECULAR SCIENCE OF MEDICINE, AICHI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454595/
关键词：
cell adhesion anti-adhesion proteglycans chondroitin osteosacoma PG-M glycocalfin annexin 58プロテイン軟骨分化

项目摘要

Cell adhesion to substrate or cell is a crucial step that regulates a variety of sell behavior. We previously showed that PG-M, a large chondroitin sulfate proteoglycan had an jnhibitory activity for any types of cell-adhesion to ECM and proposed its general role in modulating sell-ECM interactions (J.Biol. Chem., 264, 8012, 1989) Several lines of evidence suggested that the activity could be due to the chondroitin sulfate chains immobilized onto ECM via the core protein moiety. To obtain the direct evidence for the role of PG-M, we investigated the effect of the anitisense specific inhibition of PG-M synthesis on the oncogenic adhesion of human osteosarcoma cells. The inhibition suppressed the malignant cell-adhesive phenotype, consistent with the idea that PG-M controls sell-ECM adhesion. To gain insight into the mechanism, we postulated that the chondroitin sulfate-induced inhibition of sell adhesion might be due to a sell surface receptor capable of intercing specifically with chondroitin sulfate chains, thereby influencing the clustering or conformational change of receptors for ECM molecules. The present results have indicated the occurrence of a 58-kDa protein which had an affinity to the PG-M- OR chondroitin sulfate-immobilized gel column. The interaction of the protein with the column required the presence of Ca^<2+>. According to these properties, 58-kDa protein is now designated glycocalfin could be extracted with a detergent-contergent-containing solution from the membrane fractions of cultured fibroblasts and from the homogenate of minced embryo bodirs. The amino asid sequences of purified of gycocolfin have shown that this molecule is a famiry of annexin VI.Further studies of the protein will answer the question whether our postulated mechanism for the anti-adhesion actibity of immobilized chondroitin sulfate chains could be operative or not.

细胞与基质或细胞的粘附是调节多种细胞行为的关键步骤。我们先前表明PG-M（一种大的硫酸软骨素蛋白聚糖）对任何类型的细胞粘附到ECM具有抑制活性，并提出了其在调节sell-ECM相互作用中的一般作用（J. Biol. Chem.，264，8012，1989）多条证据表明，该活性可能是由于通过核心蛋白部分固定在ECM上的硫酸软骨素链造成的。为了获得PG-M作用的直接证据，我们研究了反义特异性抑制PG-M合成对人骨肉瘤细胞癌性粘附的影响。抑制抑制恶性细胞粘附表型，与PG-M控制鞍ECM粘附的想法一致。为了深入了解其机制，我们假设硫酸软骨素诱导的Sell粘附抑制可能是由于Sell表面受体能够特异性地与硫酸软骨素链相互作用，从而影响ECM分子受体的聚集或构象变化。本结果表明存在对PG-M- OR硫酸软骨素固定化凝胶柱具有亲和性的58-kDa蛋白质。蛋白质与柱的相互作用需要Ca^2+的存在。根据这些特性，58-kDa蛋白质现在被指定为glycocalfin，可以用含有洗涤剂的溶液从培养的成纤维细胞的膜部分和切碎的胚胎体的匀浆中提取。纯化的Gycocolfin的氨基酸序列表明该分子是膜联蛋白VI的一个家族。对该蛋白的进一步研究将回答我们所假设的固定化硫酸软骨素链的抗粘附活性机制是否有效的问题。