A STRESS-INDUCIBLE 72-KDA HEAT-SHOCK PROTEIN (HSP72) IS EXPRESSED ON THE SURFACE OF HUMAN TUMOR-CELLS, BUT NOT ON NORMAL-CELLS
A STRESS-INDUCIBLE 72-KDA HEAT-SHOCK PROTEIN (HSP72) IS EXPRESSED ON THE SURFACE OF HUMAN TUMOR-CELLS, BUT NOT ON NORMAL-CELLS
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DOI：
10.1002/ijc.2910610222
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发表时间：
1995-04-10
影响因子：
6.4
通讯作者：
ISSELS, RD
中科院分区：
文献类型：
--
作者：
MULTHOFF, G;BOTZLER, C;ISSELS, RD
推测热休克蛋白(HSP)70和90家族的成员参与了细胞内抗原的加工和细胞膜锚定抗原的提呈。我们发现，非致命性热休克(41.8摄氏度)在肿瘤(包括人尤文肉瘤、ES和骨肉瘤细胞HOS58)和正常细胞(包括EBV转化的B-LCL、PBL和来自健康志愿者的成纤维细胞)中都能引起类似的HSP72(约20倍)和HSP73(约3倍)的合成。然而，在37摄氏度的非致命性热应激和恢复期之后，现在用特定单抗进行的细胞学分析显示，HSP72仅在肿瘤细胞的细胞表面表达。分离膜的Western-Blot分析和HSP72特异性单抗的免疫沉淀证实了HSP72的细胞表面定位。此外，未处理的肿瘤细胞与含有HSP72的致死性热休克细胞的培养上清共同孵育，并没有导致HSP72在细胞表面的表达。因此，HSP72分子与外质膜的非特异性结合是不可能的。总之，尽管有类似的细胞质HSP72诱导，但人类肿瘤细胞在其表面表达HSP72的能力与正常细胞不同。这可能意味着临床应用作为一种以应激诱导的肿瘤特异性免疫反应为靶点的方法。(C)1995年Wiley-Liss公司
It is suggested that members of the heat-shock protein (HSP) 70 and 90 families ave involved in intracellular antigen processing and the presentation of cell-membrane-anchored antigens. We show that non-lethal heat shock (41.8 degrees C) causes comparable rates of HSP72 (about 20x) and HSP73 (about 3x) synthesis in both tumor (including human Ewing's sarcoma, ES and osteosarcoma cells, HOS58) and normal cells (including EBV-transformed B-LCL, PBL and fibroblasts derived from healthy human volunteers). However, following non-lethal heat stress and a recovery period at 37 degrees C, now cytometric analysis with a specific MAb showed HSP72 to be expressed only on the cell surface of tumor cells. The cell-surface localization of HSP72 was confirmed by Western-blot analysis of separated membranes and by immunoprecipitation with the HSP72-specific MAb. In addition, co-incubation of untreated tumor cells with supernatants from lethally heat-shocked cells, which contain HSP72, did not lead to HSP72 cell-surface expression. Thus, non-specific association of HSP72 molecules with the outer plasma membrane is unlikely. In conclusion, despite comparable cytoplasmic HSP72 induction, human tumor cells differ from normal cells in their capacity to express HSP72 on their surface. This might imply clinical application as a means to target a stress-inducible, tumor-specific immune response. (C) 1995 Wiley-Liss, Inc.