초록 ▼

1. 유방암 환자에서 혈청 리지스틴 농도가 정상인에 비해 증가하였다. (유방암 환자 17.2± 10.6 ng/mL vs. 정상인 11.3± 6.1 ng/mL, P=0.011).
2. 리지스틴은 in vitro에서 유방암 세포주 MDA-MB231의 증식이나 생존에 영향을 주지 않았으나, in vivo 이종이식 종양 모델에서 유방암의 성장을 촉진시켰다 (tumor volume, resistin group 224± 51mm3 vs. control group 107± 24 mm3, p<0.01).
3. 종양의 CD31 면역화학염

1. 유방암 환자에서 혈청 리지스틴 농도가 정상인에 비해 증가하였다. (유방암 환자 17.2± 10.6 ng/mL vs. 정상인 11.3± 6.1 ng/mL, P=0.011).
2. 리지스틴은 in vitro에서 유방암 세포주 MDA-MB231의 증식이나 생존에 영향을 주지 않았으나, in vivo 이종이식 종양 모델에서 유방암의 성장을 촉진시켰다 (tumor volume, resistin group 224± 51mm3 vs. control group 107± 24 mm3, p<0.01).
3. 종양의 CD31 면역화학염색 결과 리지스틴 군에서 대조군에 비해 미세혈관 밀도가 높았다 (microvessel density(MVD), resistin group 64± 10 MVDs/field vs. control group 37± 6 MVDs/field, p<0.01).
4. 리지스틴은 in vitro matrigel tube formation 및 scratch wound assay, 그리고 in vivo matrigel plug assay에서 일관되게 혈관신생을 촉진하였다.
5. 유방암 환자의 혈청 리지스틴 농도와 유방암 조직의 미세혈관 밀도 사이에는 유의한 상관관계가 관찰되었다 (Spearman correlation coefficient 0.537, p=0.01).
6. 리지스틴이 physiological angiogenesis 모델인 hindlimb ischemia 모델에서의 혈관신생에는 영향을 주지 않았다.

Abstract ▼

Adipokine, an adipose tissue derived hormone, is associated with cancer development and progression that is related to obesity. However, the role of resistin, a novel adipokine, which is related to both obesity and inflammation, is unclear in cancer biology. Here, we assessed the expression of resis

Adipokine, an adipose tissue derived hormone, is associated with cancer development and progression that is related to obesity. However, the role of resistin, a novel adipokine, which is related to both obesity and inflammation, is unclear in cancer biology. Here, we assessed the expression of resistin in breast cancer patients and evaluated its effects on tumor progression. We compared serum resistin levels of breast cancer patients (n=30) and healthy controls (n=30) in a case-control study and stained the tumor tissue with resistin antibody to identify the source of resistin expression. Serum resistin levels were higher in breast cancer patients than in controls (17.2± 10.6 ng/mL vs. 11.3± 6.1 ng/mL, P=0.011), but it was not expressed by cancer cells. Resistin was expressed by infiltrative monocytes in cancer tissue and the expression by monocytes was increased by interleukin-6 secreted from MDA-MB231 breast cancer cells. Using a MDA-MB231 breast cancer xenograft tumor model, we found that resistin promoted tumor growth (tumor volume, resistin group 224± 51 mm3 vs. control group 107± 24 mm3, P<0.01;tumor weight, resistin group 92± 23 mg vs. control group 56± 18 mg, P<0.05). In vitro assessment of the effect of resistin on cancer cells showed that it had no influence on the survival and proliferation of cancer cells, but increased cells’ migratory capacity. The vessel densities of the tumor tissue were assessed by CD31 immunostaining. The results suggested that the resistin increased tumor growth by angiogenesis (vessel densities, resistin group 64± 10 vessels/field vs. control group 37± 6 vessels/field, P<0.01). Furthermore, the angiogenic effect of resistin was confirmed by in vitro and in vivo angiogenesis assays, and the serum resistin levels of the breast cancer patients had a significant linear correlation with microvessel densities of their cancer tissue (Spearman correlation coefficient 0.537, P=0.01). However, resistin did not affect angiogenesis and perfusion improvement in hindlimb ischemia model, a model of physiological angiogenesis. In summary, serum resistin level is increased in breast cancer patients and promotes tumor growth by stimulating angiogenesis without any influence on physiological angiogenesis. This suggests that the resistin can be a novel therapeutic target of anti-cancer and anti-angiogenic therapy, as well as a new biomarker of tumor growth.

목차 Contents

• 표 지 ... 1
• 제출문 ... 3
• 보고서 요약서 ... 4
• 요 약 문 ... 5
• SUMMARY ... 7
• 6. 연구 성과 실적 및 향후 계획 ... 8
• 7. 참여연구원 현황표 ... 12
• II. 총괄연구과제 연구결과 ... 13
• 1. 연구개발과제의 배경 및 필요성 ... 14
• 2. 국내외 기술개발 현황 ... 15
• 3. 연구개발과제의 추진체계 ... 15
• 4. 연구개발수행 내용 및 결과 ... 16
• 5. 목표달성도 및 관련분야 기여도 ... 24
• 6. 향후 연구성과 추진 계획 ... 24
• 7. 연구개발결과의 파급효과 ... 24
• 8. 연구개발결과의 활용계획 ... 26
• 9. 연구개발과정에서 수집한 해외과학기술정보 ... 26
• 10. 참고문헌 ... 26
• 끝페이지 ... 27