Reliability of HSP70 (HSPA) expression as a prognostic marker in glioma

Abstract

Production of heat shock protein 70 (HSP70/HSPA) is induced by a wide range of cellular stress conditions, such as cancer and hypoxia, with production also being linked to tumourigenesis. HSPA mRNA transcripts and proteins were examined in three human glioma cell lines, representing astrocytoma, oligodendroglioma and glioblastoma, plus 18 clinical brain tissue samples. GAPDH was used as a control gene throughout these studies and exhibited a consistent level of expression in a normal astrocyte cell line, tumourous cell lines and tissue samples. In contrast, the average HSPA mRNA copy numbers detected in glioblastoma tissue were between 1.8- and 8.8-fold higher than in lower grade glioma and control tissue, respectively, which is suggestive of a grade-related transcription profile. Similar patterns of grade-related expression were also observed in glioma cell lines. This study indicates for the first time that HSPA expression in glioma cells may possibly be grade related, and hence could have potential as a prognostic marker.

Preclinical Models of Glioblastoma in Radiobiology: Evolving Protocols and Research Methods

“…Hypoxia also induces other signaling molecules such as heat shock protein 70 (HSP70/ HSPA). Previous evidence has shown that HSPA is present in high levels in glioma and that this correlates with tumor grade [ 16 ].…”

Immunotherapy approaches in the treatment of malignant brain tumors

“…Furthermore, HSPs within cancer cells have been associated with tumor growth and malignant phenotype . Several HSP families, including HSP70 and HSP90, are overexpressed by gliomas and, among other functions, serve to prevent stress‐induced apoptosis; HSP expression levels have been positively correlated with tumor grade . HSPs can also bind to tumor antigens to invoke an immune response …”

“…51 Several HSP families, including HSP70 and HSP90, are overexpressed by gliomas and, among other functions, serve to prevent stress-induced apoptosis; HSP expression levels have been positively correlated with tumor grade. 52 HSPs can also bind to tumor antigens to invoke an immune response. 53,54 Usually, exogenous antigens are processed by APCs through the MHC II pathway and lead to CD4-positive T-cell activation.…”

Beyond Alkylating Agents for Gliomas: Quo Vadimus?

“…Another target of interest under investigation for potential vaccination therapy is HSP. 76,77 A phase II trial (NCT01814813) is evaluating heat shock protein–peptide complex 96 (HSPPC96) with bevacizumab in patients with recurrent glioma. Similarly, IDH1 is a novel target for vaccine therapy, with one phase I trial in patients with grade III/IV glioma testing an IDH1 vaccine (NOA-16; NCT02454634).…”