Teder P, Bergh J, Heldin P
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Cancer Res. 1995 Sep 1;55(17):3908-14.
We investigated the production of hyaluronan and the presence of hyaluronan receptors in a panel of human lung carcinoma cell lines, consisting of small cell carcinomas (SCLC) and non-small cell carcinomas (non-SCLC). These transformed cell lines produced only minute amounts of hyaluronan, whereas normal lung fibroblasts synthesized high amounts. CD44 molecules (an integral membrane glycoprotein suggested previously to function as a hyaluronan receptor) were differentially expressed on non-SCLC cell lines but essentially not on the SCLC cell lines. In contrast, RHAMM molecules (receptor for hyaluronan-mediated motility) were preferentially expressed on SCLC cells. Although all the lung tumor cell lines expressed various amounts of CD44 and RHAMM, only the SCLC line U-1752 could bind [3H]hyaluronan. The binding sites were saturated with about 19,700 hyaluronan molecules (Mr 1.4 x 10(6)) bound per cell with a Kd of 0.16 x 10(-9) M. CD44 molecules were responsible for the binding activity since Hermes-1 antibodies that block the binding of hyaluronan to CD44 blocked the binding of [3H]hyaluronan to U-1752 cells. 4-Phorbol 12-myristate 13-acetate (PMA) treatment of U-1752 cells both increased the hyaluronan-binding activity in U-1752 cells as well as induced abrogation of cell-cell and cell-matrix interactions. Addition of hyaluronan inhibited the PMA-induced disassembly of the cells. The fact that CD44 molecules are able to bind [3H]hyaluronan only on the SCLC line U-1752 but not on other lung carcinoma cell lines may be of value as a marker for squamous cell carcinoma differentiation. Furthermore, the inhibitory effect of hyaluronan on the PMA-promoted cell disassembly suggest that hyaluronan surrounding squamous cell carcinoma cells may affect their migration and invasiveness.
我们研究了一组人肺癌细胞系（包括小细胞癌（SCLC）和非小细胞癌（非SCLC））中透明质酸的产生及透明质酸受体的存在情况。这些转化细胞系仅产生微量的透明质酸，而正常肺成纤维细胞则合成大量透明质酸。CD44分子（一种先前被认为作为透明质酸受体起作用的整合膜糖蛋白）在非SCLC细胞系中差异表达，但在SCLC细胞系中基本不表达。相反，RHAMM分子（透明质酸介导的运动受体）在SCLC细胞上优先表达。尽管所有肺癌细胞系都表达不同量的CD44和RHAMM，但只有SCLC细胞系U - 1752能结合[³H]透明质酸。结合位点被每个细胞约19,700个结合的透明质酸分子（Mr 1.4×10⁶）饱和，Kd为0.16×10⁻⁹M。CD44分子负责结合活性，因为阻断透明质酸与CD44结合的Hermes - 1抗体阻断了[³H]透明质酸与U - 1752细胞的结合。用4 - 佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）处理U - 1752细胞，既增加了U - 1752细胞中的透明质酸结合活性，又诱导了细胞间和细胞与基质相互作用的消除。添加透明质酸抑制了PMA诱导的细胞解离。CD44分子仅在SCLC细胞系U - 1752上而非其他肺癌细胞系上能够结合[³H]透明质酸这一事实，可能作为鳞状细胞癌分化的标志物具有价值。此外，透明质酸对PMA促进的细胞解离的抑制作用表明，围绕鳞状细胞癌细胞的透明质酸可能影响其迁移和侵袭性。
