Differential expression of versican isoforms in brain tumors
Differential expression of versican isoforms in brain tumors
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DOI：
10.1097/00005072-199605000-00005
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发表时间：
1996-05-01
影响因子：
3.2
通讯作者：
Zimmermann, DR
中科院分区：
文献类型：
--
作者：
Paulus, W;Baur, I;Zimmermann, DR
Versican是大聚集硫酸软骨素蛋白聚糖家族的成员，其是脑细胞外基质（ECM）的主要成分之一。我们研究了多功能蛋白聚糖剪接变体在mRNA和蛋白水平在正常人脑和神经胶质瘤，髓母细胞瘤，神经鞘瘤，神经纤维瘤和脑膜瘤中的表达。RT-PCR显示所有组织中V0和V1的转录本。V2 mRNA仅限于胶质瘤和正常脑组织，而V3 mRNA在除髓母细胞瘤外的所有组织中检测到。免疫组织化学使用抗体的糖胺聚糖（GAG）-α附着域的多功能蛋白聚糖（存在于V0和V2）显示减少染色的大多数胶质瘤ECM相比，正常的神经胶质瘤，而一些异常的肿瘤血管，但不是正常的脑血管，GAG-α阳性。GAG-β附着结构域（存在于V0和V1）在正常神经胶质瘤和脑血管中表达微弱，但在肿瘤血管中表达增加，并且在大多数胶质瘤ECM中不存在。GAG-α和GAG-β在所有非胶质瘤的结缔组织中均有表达。我们的数据表明，V2是正常神经胶质瘤和胶质瘤ECM的主要多功能蛋白聚糖亚型。此外，抗粘附多功能蛋白聚糖在肿瘤血管中的表达增加和在胶质瘤ECM中的表达减少可能与胶质瘤显著的局部侵袭性和颅外转移的罕见性有关。
Versican is a member of the family of large aggregating chondroitin sulfate proteoglycans which are one of the major constituents of brain extracellular matrix (ECM). We examined the expression of versican splice variants at mRNA and protein levels in normal human brain and in gliomas, medulloblastomas, schwannomas, neurofibromas, and meningiomas. RT-PCR revealed transcripts for V0 and V1 in all tissues. V2 mRNA was restricted to gliomas and normal brain, while V3 mRNA was detected in all tissues except for medulloblastomas. Immunohistochemistry using antibodies to the glycosaminoglycan (GAG)-alpha attachment domain of versican (present in V0 and V2) revealed decreased staining of most glioma ECMs compared to normal neuropil, while some abnormal tumor vessels, but not normal cerebral vessels, were GAG-alpha-positive. Expression of the GAG-beta attachment domain (present in V0 and V1) was faint in normal neuropil and cerebral vessels, but increased in tumor vessels and was absent in most glioma ECMs. Both GAG-alpha and GAG-beta were expressed in connective tissue of all nonglial tumors. Our data suggest that V2 is the major versican isoform of normal neuropil and glioma ECM. Furthermore, increased expression in tumor vessels and decreased expression in glioma ECM of the anti-adhesive versican may be related to marked local invasivity and rarity of extracranial metastasis of gliomas.