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.
Bibliographical noteFunding Information:
This research was supported by KHIDI (HI14C3319), KIST Institutional Programs (2V03110), National Research Council of Science & Technology (NST, CRC-15-04-KIST), and Basic Science Research Program through the National Research Foundation of Korea (NRF, 2015R1A6A3A04058568) funded by the Ministry of Education, Science and Technology. The authors would like to thank Dr. Nakwon Choi (KIST) for providing a confocal microscope and Dr. Jiyeon Lee (KIST) for providing a fluorescent microscope.
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