Abstract
High-grade glioma is a highly malignant and metastatic brain cancer, resistant to many existing anticancer treatments. In such glioma cancer cells, the glucose-regulated protein 78 kDa (GRP78) is particularly highly up-regulated. Former studies have thus targeted mutation-free GRP78 not only to detect glioma cancer cells specifically but also to enhance cytotoxic effect. We focus on cell surface-expressed GRP78 as a target for suppressing high-grade glioma cell lines. Glioblastoma multiforme (GBM) cell line, highly malignant glioma cells, was first injected into 5-week-old athymic mice to confirm and compare GRP78 expression in vivo in xenografted and normal brain tissue. Immunofluorescence and immunoblotting were utilized to detect surface-localized GRP78 in diverse high-grade glioma cell lines. By treating glioma cell lines with the polyclonal N-20 antibody against surface-localized GRP78, we subsequently studied the significance of surface GRP78 to the survival and growth of the glioma cell lines. We found that inhibiting the function of surface GRP78 suppressed cancer cell survival and growth proving that the surface-expressed GRP78 is a vital receptor involved in the proliferation of high-grade glioma. Our findings provide opportunities to target surface GRP78 as a biomarker for high-grade glioma and to develop effective cell-specific anticancer therapy.
Highlights
Despite advances in anticancer therapy, glioma remain difficult to treat
We found a high expression of glucose-regulated protein 78 kDa (GRP78) in the glioblastoma multiforme (GBM) of the brains of xenografted mice 28 days post-injection (Fig. 1C), indicating that the up-regulation of GRP78 in high-grade glioma cell lines is likewise shown in xenografted animal models
It has been reported that GRP78 expression increases with pathologic grade level of glioma[13]
Summary
The complex multiforme nature – the genetic heterogeneity and pleomorphic cells – make the tumour difficult to target and highly resistant to current cancer therapies. Suppression of tumour survival and growth through receptor inhibition is a promising method to potentially treat gliomas Such invasive characteristics of glioma are known to be regulated by the glucose-regulated protein 78 kDa (GRP78), a member of the heat shock protein 70 family. Recent studies have found highly elevated GRP78 expression in tumour microenvironments, resulting in active translocation of GRP78 to the surface of cancer cells[3]. It is on the surface of highly invasive tumour cells where GRP78 has been postulated to assume proliferative roles[4]. The significance of surface GRP78 in tumour survival and growth, we treated the high-grade glioma cell lines with a polyclonal antibody N-20 against surface GRP78, thereby neutralizing its function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
