D'Abaco Giovanna M, Ng Ken, Paradiso Lucy, Godde Nathan J, Kaye Andrew, Novak Ulrike
Department of Surgery, Royal Melbourne Hospital, Parkville, Australia.
Neurosurgery. 2006 Jan;58(1):179-86; discussion 179-86. doi: 10.1227/01.neu.0000192363.84287.8b.
To study the expression and function of the brain-specific proteinase deficient disintegrins, ADAM11 and ADAM22 (a disintegrin and metalloproteinase).
Specimens of low- and high-grade gliomas and normal brain were analyzed for ADAM11 and ADAM22 expression using Western blotting. The effects of overexpression of ADAM11 and ADAM22 in glioma cells on growth were analyzed using bromodeoxyuridine incorporation linked to immunocytochemistry. Similarly analyzed were the effects on cell proliferation of bacterially expressed glutathione S-transferase fusion proteins with the disintegrin domain of ADAM11 and ADAM22.
ADAM22 is expressed in normal brain and some low-grade gliomas, but not in high-grade gliomas, whereas ADAM11 is expressed in all low- and high-grade gliomas. In vitro, ADAM22 inhibits cellular proliferation of glioma derived astrocytes. The growth inhibition appears to be mediated by interactions between the disintegrin domain of ADAM22 and specific integrins expressed on the cell surface. This growth inhibition can be avoided by over-expression of integrin linked kinase.
ADAM22, a brain-specific cell surface protein, mediates growth inhibition using an integrin dependent pathway. It is expressed in normal brain but not in high-grade gliomas. A related protein, ADAM11, has only a minor effect on cell growth, and its expression is unchanged in low- and high-grade gliomas.
研究脑特异性蛋白酶缺陷型解整合素金属蛋白酶11（ADAM11）和ADAM22的表达及功能。
采用蛋白质免疫印迹法分析低级别和高级别胶质瘤标本以及正常脑组织中ADAM11和ADAM22的表达。利用与免疫细胞化学相关的溴脱氧尿苷掺入法分析ADAM11和ADAM22在胶质瘤细胞中的过表达对生长的影响。同样分析了带有ADAM11和ADAM22解整合素结构域的细菌表达谷胱甘肽S-转移酶融合蛋白对细胞增殖的影响。
ADAM22在正常脑组织和一些低级别胶质瘤中表达，但在高级别胶质瘤中不表达，而ADAM11在所有低级别和高级别胶质瘤中均有表达。在体外，ADAM22抑制胶质瘤来源星形胶质细胞的细胞增殖。这种生长抑制似乎是由ADAM22的解整合素结构域与细胞表面表达的特定整合素之间的相互作用介导的。通过整合素连接激酶的过表达可以避免这种生长抑制。
ADAM22是一种脑特异性细胞表面蛋白，通过整合素依赖性途径介导生长抑制。它在正常脑组织中表达，但在高级别胶质瘤中不表达。一种相关蛋白ADAM11对细胞生长只有轻微影响，其在低级别和高级别胶质瘤中的表达没有变化。
