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기질 세포에 의해 유도되는 위암 복막 전이에서 discoidin domain receptor 1의 역할에 대한 연구
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 허훈 | - |
| dc.contributor.author | 진혜진 | - |
| dc.date.accessioned | 2019-10-21T07:30:33Z | - |
| dc.date.available | 2019-10-21T07:30:33Z | - |
| dc.date.issued | 2017-08 | - |
| dc.identifier.other | 25572 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/19074 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2017. 8 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 II. MATERIALS AND METHODS 3 1. Human samples and immunohistochemical staining 3 2. Cell lines and chemicals 3 3. CRISPR/Cas9-mediated knockout of DDR1 4 4. Western blot 5 5. Cell viability test 5 6. RT-PCR 6 7. Organotypic culture and immunocytochemical staining 6 8. Peritoneal xenograft mouse models 6 9. Statistical analysis 7 III. RESULTS 8 1. DDR1 expression correlates with peritoneal recurrence in primary GC tissues 8 2. CAFs enhance the peritoneal tumorigenic potential of GCs 11 3. CAFs-induced upregulation of DDR1 in GC cell lines 14 4. DDR1 inhibition using the CRISPR/Cas9 system suppresses the effects of CAFs 20 5. Blocking DDR1 signaling through 7rh represses the effects of CAFs on GCs 22 IV. DISCUSSION 30 V. REFERENCES 35 국문요약 42 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | 기질 세포에 의해 유도되는 위암 복막 전이에서 discoidin domain receptor 1의 역할에 대한 연구 | - |
| dc.title.alternative | Inhibition of discoidin domain receptor 1 prevents stroma-induced peritoneal metastasis in gastric carcinomas | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Hyejin Jin | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2017. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 788572 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025572 | - |
| dc.subject.keyword | Gastric carcinomas | - |
| dc.subject.keyword | Peritoneal metastasis | - |
| dc.subject.keyword | Discoidin domain receptor | - |
| dc.subject.keyword | Cancer-associated fibroblasts | - |
| dc.description.alternativeAbstract | Although the interactions between cancer cells and the tumor stroma are known to play a role in the peritoneal metastasis of gastric carcinomas (GCs), effective targeting agents that block these interactions have never been reported. Discoidin domain receptor 1 (DDR1) is activated by triple-helix collagens, which are major components of tumor stroma; thus, DDR1 might have a key role in the communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in GCs. Methods: We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in GC tissues from a cohort established in a previous study. We also co-cultured human GC cell lines with gastric cancer-associated fibroblasts (CAFs), and investigated DDR1 expression and activation by western blotting. We evaluated the CAF-induced tumorigenic ability of GC cell lines and the effects of a DDR1-specific inhibitor in organotypic cultures and a peritoneal seeding xenograft animal model. Results: The expression of DDR1 in gastric cancer tissues was significantly positively associated with early recurrence (p = 0.043) and a high incidence of peritoneal recurrence (p = 0.036). We confirmed that co-culture with CAFs elevated DDR1 protein expression in GC cell lines. CAFs also enhanced GC cell line spheroid formation in organotypic cultures in a tumor cell DDR1-dependent manner. Co-implantation of CAFs with GC cells enhanced peritoneal tumor formation in vivo, an effect that was sensitive to pharmacologic inhibition of DDR1. Conclusion: Our findings suggest that the CAF-induced elevation of DDR1 in GC cells enhances their peritoneal tumorigenesis, and that the inhibition of DDR1 signaling is an attractive strategy for the treatment of GC peritoneal metastasis. | - |
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