초록 ▼

간암관련 시알산당쇄합성효소 및 당쇄 $\alpha$2-8 sialic acid 함유 sialo-glyco-epitope 생합성 sialyltransferase 해석. 간암의 E-selectin에 대한 sialyl-LeX 결정기 확인. 간암침윤에서 E-selectin counter-receptor로 sialyl-Lea 결정기와 간암세포에서 galactose에 $\alpha$2-3 결합 sialic acid 증가확인. 임상연구로 sialyl lewis A항원증가 확인. sialyl lewis 항원

간암관련 시알산당쇄합성효소 및 당쇄 $\alpha$2-8 sialic acid 함유 sialo-glyco-epitope 생합성 sialyltransferase 해석. 간암의 E-selectin에 대한 sialyl-LeX 결정기 확인. 간암침윤에서 E-selectin counter-receptor로 sialyl-Lea 결정기와 간암세포에서 galactose에 $\alpha$2-3 결합 sialic acid 증가확인. 임상연구로 sialyl lewis A항원증가 확인. sialyl lewis 항원용 ST3Gal III, FUT III 및 VII유전자발현증가확인. 간암세포에서 sialyl lewis A항원 증가 검정. 간암세포의 TNF-a-자극 endothelial세포와 접착증가, Sialyl lewis X-A 항원 결합 E-selectin 길항올리고당으로 sialic acid함유 GM3와 sialyl lactose의 발굴과 VEGFR2상호작용발굴 성공. 길항올리고당으로 sialic acid함유 GM3와 sialyl lactose의 VEGF-유도증식, 튜브형성 및 HUVEC이동억제. VEGF-매개 신호전달 경로억제 및 VEGF-유도 혈관신생 in vivo 억제확인.

Abstract ▼

Change of the cell surface glycosylation is one of the most important modifications that occur in cellular transformation such as oncogenesis. Both glycoproteins and glycolipids carbohydrate moieties are affected by cellular transformation, leading to the appearance of carbohydrate tumor associated

Change of the cell surface glycosylation is one of the most important modifications that occur in cellular transformation such as oncogenesis. Both glycoproteins and glycolipids carbohydrate moieties are affected by cellular transformation, leading to the appearance of carbohydrate tumor associated antigens (CTAA). These changes in glycosylation have been described for a large number of cancer types and are usually associated with a poor prognosis for the patients. Most of the CTAA are sialylated antigens and the increase of sialylation is a well-known general feature of transformed cells. As an example, the mucin-type Sialyl-Tn antigen is increase in liver cancers and associated with a poor prognosis for the patients. Modifications of cellular glycosylation are a common phenotypic change in malignancy. The adhesion of malignant cells to vascular endotheliumis an important step for extravasation into target tissues of new organ. Malignant transformation is associated with abnormal glycosylation, resulting in the synthesis and expression of altered carbohydrate determinants on protein or lipid. Expression of carbohydrate determinants such as sialyl lewis A and sialyl lewis X is markedly enhanced in cancer cells. Sialyl lewis A and sialyl lewis X are involved in E-selectin-mediated adhesion of cancer cells to vascular endothelium, and these determinants play important roles in hematogenous metastasis of liver cancer cells. We confirmed the relationship between HBx and sialyl lewis X/A in liver cancer patients, and investigated whether HBx induces the expression of sialyl lewis X/A in liver cells and hepatocarcinoma patients. Additionally, we examined whether the liver cancer cell adhesion is mediated by sialyl lewis X/A to endothelial cells for metastatic step. We have shown for the first time that sialyl lewis X/A plays important role in the induction of metastatic potential by expression of e-selectin of cytokines-stimulated endothelial cell. Inaddition, monosialic acid-containing GM3 inhibited the proliferation, migration and tube formation of endothelial cell by suppressing the activation of the VEGF receptor-2 (VEGFR-2), and its downstream signal in response to VEGF. GM3 significantly blocked VEGF-stimulated neovascularization in matrigel plugs and chorioallantoic membrane assays. These results indicate that monosialic acid-containing GM3 actsas a negative angiogenic factor in angiogenesis in vivo as well as in vitrofor tumor regression.

목차 Contents

• 표지...1
• 제출문...3
• 보고서 요약서...4
• 요약문...5
• SUMMARY...7
• 연구 성과 실적 및 향후 계획...8
• 참여연구원 현황표...16
• II. 총괄연구과제 연구결과...17
• 1. 연구개발과제의 배경 및 필요성...18
• 2. 국내외 기술개발 현황...30
• 3. 연구개발과제의 추진체계...35
• 4. 연구개발수행 내용 및 결과...36
• 5. 목표달성도 및 관련분야 기여도...50
• 5.1. 총괄연구개발과제의 목표달성도...50
• 5.2. 관련분야 기여도...51
• 6. 향후 연구성과 추진 계획...51
• 7. 연구개발결과의 파급효과...51
• 7.1. 기술적 파급효과...52
• 7.2. 경제.산업적 파급효과...52
• 7.3. 사회적 파급효과...52
• 8. 연구개발결과의 활용계획...53
• 8.1. 연구개발결과의 활용계획 및 추가연구의 필요성...53
• 8.2. 사업화(기업화) 목표 달성도 및 계획...53
• 8.3. 사업화 수준(계획 및 완료 포함)...53
• 9. 연구개발과정에서 수집한 해외과학기술정보...53
• 10. 참고문헌...53
• IV. 첨부서류...56
• 1. 자체평가의견서...58
• 2. 실적 증빙자료...63
• 3. 기타 첨부서류...64