ABSTRACT
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 Hsp90ß, we showed that membrane-bound Hsp90α and Hsp90ß 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 Hsp90ß to the plasma membrane.
Subject(s)
Fibrosarcoma/metabolism , Glioblastoma/metabolism , HSP90 Heat-Shock Proteins/biosynthesis , Protein Isoforms/biosynthesis , Biophysical Phenomena , Cell Line, Tumor , Cell Membrane/metabolism , Cell Movement/genetics , Fibrosarcoma/pathology , Glioblastoma/pathology , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Heparan Sulfate Proteoglycans , Humans , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Protein Binding , Protein Isoforms/genetics , Protein Isoforms/metabolismABSTRACT
We studied the effect of purified native heat shock protein 90 (Hsp90) from bovine and mouse brain on migration and invasion of human glioblastoma (A-172) and fibrosarcoma (HT1080) cells. Hsp90 in concentrations of 0.01-0.10 mg/ml stimulated migration and invasion of tumor cells in vitro by 20-32% (p<0.05). Polyclonal antibodies to Hsp90 blocked the Hsp90-dependent stimulation of cell invasion, which indicates specificity of the stimulating effect of extracellular Hsp90 on tumor cell invasion. Hence, extracellular Hsp90 can be considered as a promising molecular target, because its inhibition can suppress invasion and metastasizing of tumor cells.
Subject(s)
Fibroblasts/drug effects , HSP70 Heat-Shock Proteins/pharmacology , HSP90 Heat-Shock Proteins/pharmacology , Neuroglia/drug effects , Animals , Antibodies/pharmacology , Brain Chemistry , Cattle , Cell Line, Tumor , Cell Movement/drug effects , Diffusion Chambers, Culture , Extracellular Matrix Proteins/pharmacology , Fibroblasts/cytology , HSP70 Heat-Shock Proteins/antagonists & inhibitors , HSP70 Heat-Shock Proteins/isolation & purification , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/isolation & purification , Mice , NIH 3T3 Cells , Neuroglia/cytologyABSTRACT
AIM: To evaluate the clinical efficiency of using autologous conditioned (activated) serum (ACS) versus hyaluronic acid (HA) in coxarthrosis (CA). SUBJECTS AND METHODS: Two groups of patients (n = 54) who were matched for age, sex, and disease duration and had a valid diagnosis of CA were examined. During 3 weeks, Groups 1 and 2 patients received intra-articular therapy with ACS or synocrome forte (Croma Pharma, Sotex), respectively, for 3 weeks. A 12-month follow-up evaluated the magnitude of pain, by using the visual analog scale (VAS, mm), the functional index WOMAC and general health, by applying the EQ-VAS scale. RESULTS: The only benefit of HA was found to be more functional improvement as detected by the WOMAC index (-21.8%; t = 2.56) at an early (1-month) follow-up. After 3 months, the patients in the ACS group were recorded to have the maximum VAS pain intensity reduction that was 76.5% greater than that (t = 4.31) in the HA group. The clearest advantages of ACS therapy were traced 6 months after treatment. CONCLUSION: The use of ACS may be a real alternative to that of HA derivatives in achieving good clinical outcomes in patients with CA. After ACS administration, there was a long-term preservation of achieved positive results.
Subject(s)
Hyaluronic Acid/administration & dosage , Osteoarthritis, Hip/therapy , Serum , Viscosupplements/administration & dosage , Aged , Female , Humans , Injections, Intra-Articular , Male , Middle Aged , Osteoarthritis, Hip/blood , Severity of Illness Index , Treatment Outcome , Viscosupplements/bloodABSTRACT
The influence ofplatelet-enriched plasma (PEP) ofpain intensity was estimated using a visual-analogous scale and the Wormac questionnaire in patients with knee osteoarthrosis (KOA). Beneficial effect on all variables studied was documented within I month after the onset of therapy. It was totally absent after 3 months in severe KOA but was apparent in typical KOA. Positive dynamics throughout months 1 and 3 was observed only in patients with early manifestations of KOA. It persisted during all 12 months of the study.
Subject(s)
Osteoarthritis, Knee/complications , Pain Management/methods , Pain/etiology , Platelet-Rich Plasma , Adult , Aged , Female , Humans , Male , Middle Aged , Pain Measurement , Severity of Illness Index , Surveys and Questionnaires , Time FactorsABSTRACT
We studied clinical and psychosomatic characteristics in 34 patients with rheumatoid arthritis. Sixteen patients received Vozraston (without considering the individual sensitivity) in addition to standard therapy. No changes in clinical and psychoemotional parameters were revealed. Vozraston reduced pain syndrome and increased the tone of the sympathetic nervous system.
