Herold-Mende Christel, Mueller Margareta M, Bonsanto Mario M, Schmitt Horst Peter, Kunze Stefan, Steiner Hans-Herbert
Molecular Biology Laboratory, Neurosurgery Hospital, University of Heidelberg, Germany.
Int J Cancer. 2002 Mar 20;98(3):362-9. doi: 10.1002/ijc.10233.
The extracellular matrix protein tenascin-C is expressed in processes like embryogenesis and wound healing and in neoplasia. Tenascin-C expression in gliomas has been described previously; however, the relation to clinical data remains inconsistent. Generally, analysis of tenascin-C function is difficult due to different alternatively spliced isoforms. Our studies focus on changes in tenascin-C expression in human gliomas, correlating these changes with tumor progression and elucidating the functional role of the glioma cell-specific tenascin-C isoform pool. Eighty-six glioma tissues of different World Health Organization (WHO) grades were analyzed immunohistochemically for tenascin-C expression. The influence of the specific tenascin-C isoforms produced by glioblastoma cells on proliferation and migration was examined in vitro using blocking antibodies recognizing all isoforms. In general, tenascin-C expression increased with tumor malignancy. Perivascular staining of tenascin-C around tumor-supplying blood vessels was observed in all glioblastoma tissues, whereas in WHO II and III gliomas, perivascular tenascin-C staining appeared less frequently. The appearance of perivascular tenascin-C correlated significantly with a shorter disease-free time. Analysis of proliferation and migration in the presence of blocking antibodies revealed an inhibition of proliferation by around 30% in all 3 glioblastoma cell cultures, as well as a decrease in migration of 30.6-46.7%. Thus we conclude that the endogenous pool of tenascin-C isoforms in gliomas supports both tumor cell proliferation and tumor cell migration. In addition, our data on the perivascular staining of tenascin-C in WHO II and III gliomas and its correlation with a shorter disease-free time suggest that tenascin-C may be a new and potent prognostic marker for an earlier tumor recurrence.
细胞外基质蛋白腱生蛋白-C在胚胎发生、伤口愈合以及肿瘤形成等过程中表达。此前已有关于腱生蛋白-C在胶质瘤中表达的描述；然而，其与临床数据的关系仍不一致。一般来说，由于存在不同的可变剪接异构体，分析腱生蛋白-C的功能较为困难。我们的研究聚焦于人类胶质瘤中腱生蛋白-C表达的变化，将这些变化与肿瘤进展相关联，并阐明胶质瘤细胞特异性腱生蛋白-C异构体库的功能作用。对86个不同世界卫生组织（WHO）分级的胶质瘤组织进行免疫组织化学分析，以检测腱生蛋白-C的表达。使用识别所有异构体的阻断抗体在体外研究胶质母细胞瘤细胞产生的特定腱生蛋白-C异构体对增殖和迁移的影响。总体而言，腱生蛋白-C的表达随肿瘤恶性程度增加而升高。在所有胶质母细胞瘤组织中均观察到肿瘤供血血管周围有腱生蛋白-C的血管周围染色，而在WHO II级和III级胶质瘤中，血管周围腱生蛋白-C染色出现的频率较低。血管周围腱生蛋白-C的出现与无病生存期缩短显著相关。在存在阻断抗体的情况下对增殖和迁移进行分析发现，在所有3种胶质母细胞瘤细胞培养物中，增殖受到约30%的抑制，迁移减少了30.6 - 46.7%。因此我们得出结论，胶质瘤中腱生蛋白-C异构体的内源性库支持肿瘤细胞增殖和肿瘤细胞迁移。此外，我们关于WHO II级和III级胶质瘤中腱生蛋白-C血管周围染色及其与较短无病生存期相关性的数据表明，腱生蛋白-C可能是肿瘤早期复发的一种新的强效预后标志物。
