원문정보
초록
영어
CD24 is a glycosylphosphatidylinositol(GPI)-anchored membrane protein which consists of a
small protein core comprising 27 amino acids and is extensively glycosylated. Almost half of the
amino acid in CD24 are composed of Ser and Thr residues which can be potential sites for Olinked glycans. CD24, originally described as a B cell marker, started drawing considerable
attention as anti-cancer target showing that CD24 overexpressions in many carcinomas are
significantly associated with a more aggressive course of the disease. In our previous studies, we found that expression of CD24 in ovarian cancer had association with tumor grade and stage. In this study, we tried to validate CD24 as anti-cancer target in ovarian cancer. From microarray
result, ovarian cancer had the most relevant CD24 overexpression level difference from normal. To study CD24 targeting effect in ovarian cancer, we screened CD24 overexpression cell with various method like RT-PCR, qPCR, WB, FACS. And then ADCC and CDC effects, which were
considered as major mechanism for mAb therapeutic effect, were measured with CD24
overexpression cells, OVCAR3 and SK-OV3 using commercial anti-CD24 mAb, SN3. Targeting
of CD24 in those cell lines showed dramatic cytotoxic effects more than 50% through natural
immune system, ADCC and CDC. Another mechanism for anti-cancer effect, which we have
taken notice, is P-selectin binding to cancer cell via CD24 which could facilitate cancer metastasis. From this point of view, Anti-CD24 mAb could also play a metastasis-inhibiting role by preventing CD24 from binding to P-selectin. Practically, we confirmed that CD24 could interact to P-selectin from sandwich ELISA and FACS. Based on these results, we will have further study to confirm anti-metastatic effect of CD24 mAb in ovarian cancer metatastasis mouse model. Finally we conducted in vivo experiment with human ovarian cancer xenograft nude mouse. We observed that mouse with treatment of anti-CD24 antibody had a propensity to decrease the tumor growth rate compared with control group treated with PBS. In conclusion, CD24 may have possibility as a validated target for monoclonal antibody therapy in ovarian carcinoma.