The Role of Membrane-Bound Heat Shock Proteins Hsp90 in Migration of Tumor Cells in vitro and Involvement of Cell Surface Heparan Sulfate Proteoglycans in Protein Binding to Plasma Membrane

• Published in: Biofizika Vol. 61; no. 2; p. 328
• Main Authors: Snigireva, A V, Vrublevskaya, V V, Skarga, Y Y, Morenkov, O S
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-03-2016
• Subjects: Biophysical Phenomena; Cell Line, Tumor; Cell Membrane - metabolism; Cell Movement - genetics; Fibrosarcoma - metabolism; Fibrosarcoma - pathology; Glioblastoma - metabolism; Glioblastoma - pathology; Heparan Sulfate Proteoglycans; HSP90 Heat-Shock Proteins - biosynthesis; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Humans; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Protein Binding; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Protein Isoforms - metabolism
• ISSN: 0006-3029

Heat shock protein Hsp90, detected in the extracellular space and on the membrane of cells, plays an important role in cell motility, migration, invasion and metastasis of tumor cells. At present, the functional role and molecular mechanisms of Hsp90 binding to plasma membrane are not elucidated. Using isoform-specific antibodies against Hsp90, Hsp9α and Hsp90β, we showed that membrane-bound Hsp90α and Hsp90β play a significant role in migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Disorders of sulfonation of cell heparan sulfates, cleavage of cell heparan. sulfates by heparinase I/III as well as treatment of cells with heparin lead to an abrupt reduction in the expression level of Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. The results obtained demonstrate that two isoforms of membrane-bound Hsp90 are involved in migration of tumor cells in vitro and that cell surface heparan sulfate proteoglycans play a pivotal role in the "anchoring" of Hsp90α and Hsp90β to the plasma membrane.