| Abstract: | The heat-shock protein Hsp90, which is found in the extracellular space and on the cell membrane, plays an important role in cell motility, migration, invasion, and metastasis of tumor cells. Currently, the functional role and molecular mechanisms of Hsp90 binding to the plasma membrane are not clear. Using isoform-specific antibodies against Hsp90, Hsp90α, and Hsp90β, we showed that the membrane-bound Hsp90α and Hsp90β proteins play a significant role in the migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Impairment of sulfonation of cellular heparan sulfates, cleavage of cellular heparan sulfates by heparinase I/III, as well as the treatment of cells with heparin, lead to a dramatic reduction in the expression levels of the Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. These results demonstrate that two isoforms of membrane-bound Hsp90 are involved in tumor-cell migration in vitro. As well, the cell surface heparan sulfate proteoglycans are shown to play a pivotal role in the “anchoring” of Hsp90α and Hsp90β to the plasma membrane. |
