title: Cell surface GRP78 as a biomarker and target for suppressing glioma cells.
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.
authors.affiliation: Convergence Research Center for Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Kang
authors.affiliation: Convergence Research Center for Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Convergence Research Center for Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Republic of Korea.|Department of Neuroscience, Princeton University, New Jersey, USA.
authors.forename: Bo-Ryehn
authors.initials: BR
authors.lastname: Chung
authors.affiliation: Convergence Research Center for Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Woong
authors.initials: W
authors.lastname: Kim
authors.affiliation: Convergence Research Center for Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Republic of Korea.|Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: YoungSoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D019138:Antibodies, Blocking; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse