Kaaijk P, Troost D, Morsink F, Keehnen R M, Leenstra S, Bosch D A, Pals S T
Department of Neurosurgery, University of Amsterdam, Netherlands.
J Neurooncol. 1995 Dec;26(3):185-90. doi: 10.1007/BF01052621.
Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of CD44 variant exon encoded sequences (CD44v) in primary brain tumors in situ has not been studied in detail. In the present study, the expression of CD44s and CD44v epitopes was analyzed immunohistochemically on frozen sections of primary brain tumors. In addition, the expression of CD44 on cultured glioma cells was investigated by immunofluorescence flow cytometry. The results demonstrate the presence of CD44s epitopes and of CD44 splice variants containing CD44v4, v5 and v10 sequences in various types of brain tumors. A subgroup of highly malignant gliomas showed a strong (focal) expression of CD44v5. CD44v6 was absent in all brain tumors examined. CD44s appeared to be the dominant form of CD44 expressed in primary brain tumors, its expression was not correlated with tumor grade. We envisage that CD44 isoforms, in particular CD44s, may contribute to the invasive character of primary tumors by interacting with hyaluronate, one of the most abundant molecules in the extracellular matrix of the brain.
CD44的表达,尤其是某些剪接变体的表达,已与多种不同动物和人类癌症中的肿瘤进展和转移潜能相关联。尽管已有报道人类脑肿瘤中CD44标准表位(CD44s)存在差异表达,但原发性脑肿瘤原位中CD44可变外显子编码序列(CD44v)的表达尚未得到详细研究。在本研究中,通过免疫组织化学方法对原发性脑肿瘤冰冻切片上CD44s和CD44v表位的表达进行了分析。此外,通过免疫荧光流式细胞术研究了培养的胶质瘤细胞上CD44的表达。结果表明,在各种类型的脑肿瘤中存在CD44s表位以及包含CD44v4、v5和v10序列的CD44剪接变体。一组高度恶性的胶质瘤显示出CD44v5的强(局灶性)表达。在所检查的所有脑肿瘤中均未检测到CD44v6。CD44s似乎是原发性脑肿瘤中表达的CD44的主要形式,其表达与肿瘤分级无关。我们设想,CD44异构体,特别是CD44s,可能通过与透明质酸相互作用,促进原发性肿瘤的侵袭性,透明质酸是脑细胞外基质中最丰富的分子之一。