Sherman L, Skroch-Angel P, Moll J, Schwechheimer K, Ponta H, Herrlich P, Hofmann M
Institut für Genetik, Kernforschungszentrum Karlsruhe, Germany.
J Neurooncol. 1995 Dec;26(3):171-84. doi: 10.1007/BF01052620.
Members of the CD44 family of cell surface hyaluronate-binding proteins have been implicated in cell migration, cell-matrix interactions and tumor progression. To determine whether these proteins might play a role in the normal functions of Schwann cells and in their tumorigenesis, we examined the patterns of CD44 expression in Schwann cells from rat peripheral nerve, rat Schwann cell tumor lines, and human schwannomas. Normal rat spinal nerves and primary Schwann cell cultures expressed standard CD44 (CD44s) but not alternatively spliced variant isoforms. In contrast, rat Schwann cell tumor lines expressed both CD44s and a number of variants, including proteins containing sequences encoded by exon v6. Furthermore, we found that these cell lines bind hyaluronate, and that their cell surface hyaluronate binding correlates with CD44 expression. All of the human schwannomas also expressed CD44 variants, especially epitopes encoded by exon v5, the border between v7 and v8, and v9-10. These data indicate that Schwann cells normally express CD44s, that Schwann cell tumors express both CD44s and particular variants of CD44, and that CD44s and possibly variants of CD44 are involved in hyaluronate recognition by Schwann cell tumors.
细胞表面透明质酸结合蛋白CD44家族的成员与细胞迁移、细胞-基质相互作用及肿瘤进展有关。为了确定这些蛋白是否可能在雪旺氏细胞的正常功能及其肿瘤发生过程中发挥作用,我们检测了大鼠外周神经雪旺氏细胞、大鼠雪旺氏细胞瘤细胞系及人类神经鞘瘤中CD44的表达模式。正常大鼠脊神经和原代雪旺氏细胞培养物表达标准CD44(CD44s),但不表达可变剪接的变异体亚型。相反,大鼠雪旺氏细胞瘤细胞系同时表达CD44s和多种变异体,包括含有外显子v6编码序列的蛋白。此外,我们发现这些细胞系能结合透明质酸,且它们的细胞表面透明质酸结合与CD44表达相关。所有人类神经鞘瘤也表达CD44变异体,尤其是外显子v5、v7与v8之间的边界以及v9 - 10编码的表位。这些数据表明,雪旺氏细胞正常表达CD44s,雪旺氏细胞瘤同时表达CD44s和特定的CD44变异体,且CD44s以及可能的CD44变异体参与雪旺氏细胞瘤对透明质酸的识别。