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Inhibiting the GAS6/AXL axis suppresses stroma-induced progression in gastric carcinoma
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 허훈 | - |
| dc.contributor.author | 배청아 | - |
| dc.date.accessioned | 2019-04-01T16:40:43Z | - |
| dc.date.available | 2019-04-01T16:40:43Z | - |
| dc.date.issued | 2019-02 | - |
| dc.identifier.other | 28785 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/14930 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2019. 2 | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 II. MATERIALS AND METHODS 3 1. Cell culture 3 2. RNA isolation and quantitative real-time PCR (qRT-PCR) 3 3. Western blotting 4 4. Immunohistochemical staining 5 5. Immunocytochemical staining 6 6. Transwell migration assay 6 7. Cell proliferation assay 7 8. shRNA-mediated knockdown of AXL 7 9. Intraperitoneal xenograft mouse models 8 10. Reverse transcription polymerase chain reaction (RT-PCR) 8 11. Collection of GC gene expression datasets 9 12. Statistical analysis 9 III. RESULTS 10 1. CAFs are the main source of GAS6 in the GC microenvironment and CAFproduced GAS6 activates AXL in GC cells 10 2. CAFs increase cell motility and proliferation through the GAS6/AXL axis 16 3. AXL inhibitor rescues CAF-induced aggressive phenotype of GC cells 26 4. Expression of GAS6/AXL axis in human GC tissues 34 IV. DISCUSSION 38 V. REFERENCES 42 국문요약 47 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Inhibiting the GAS6/AXL axis suppresses stroma-induced progression in gastric carcinoma | - |
| dc.title.alternative | Cheong A Bae | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Cheong A Bae | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2019. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 905267 | - |
| dc.identifier.uci | I804:41038-000000028785 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/common/orgView/000000028785 | - |
| dc.description.alternativeAbstract | Introduction: Cancer-associated fibroblasts (CAFs) are a major component of tumor stroma and their effect on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAFs and GC cells have not been applied in a clinical setting. Growth arrest-specific 6 (GAS6) is a major ligand of AXL receptor tyrosine kinase (AXL) and its binding is essential for activation of AXL. In the present study, we found that, in the GC microenvironment, GAS6 mainly originates from CAFs. Thus, AXL might have a key role in the communication between cancer cells and CAFs. The aim of this study was to investigate the effect of an AXL inhibitor on CAF-induced GC progression. Methods: We examined GAS6 and AXL expression in various cell lines, including GC cells and non-cancerous cells, by qRT-PCR and western blotting. We also co-cultured human GC cells with CAFs and investigated phosphorylation of AXL by western blotting and immunocytochemistry. We evaluated the role of CAF-derived GAS6 on the motility, proliferation, and tumorigenic ability of GC cells. The effect of the AXL-specific inhibitor, BGB324, on the CAF-induced aggressive phenotype of GC cells was also investigated. Finally, we performed immunohistochemistry to measure the phosphorylation of AXL in a tissue microarray composed of 175 GC tissues, and evaluated its correlation with the prognosis of GC patients. Results: qRT-PCR and western blotting showed that GAS6 expression was higher in CAFs relative to other cells. We found that CAFs increased the phosphorylation of AXL, differentiation into a mesenchymal-like phenotype, and proliferation in GC cells. Co-implantation of CAFs with GC cells enhanced peritoneal tumor formation in vivo. When the expression of AXL was inhibited in GC cells, the effect of CAF was reduced. In addition, BGB324, a small molecule inhibitor of AXL, suppressed the effects of CAFs on GC cells. In GC tissues, a high level of phosphorylated AXL were significantly associated with poor overall survival (P = 0.022). Conclusion: Above findings indicated that the CAF-induced activation of AXL in GC cells was significantly associated with poor prognosis of GC patients. We conclude that an AXL inhibitor may be a novel agent for GC treatment. | - |
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- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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