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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃敏銓 | zh_TW |
| dc.contributor.advisor | Min-Chuan Huang | en |
| dc.contributor.author | 陳儷元 | zh_TW |
| dc.contributor.author | Li-Yuan Chen | en |
| dc.date.accessioned | 2025-02-20T16:29:36Z | - |
| dc.date.available | 2025-02-21 | - |
| dc.date.copyright | 2025-02-20 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2025-01-02 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96677 | - |
| dc.description.abstract | 頭頸部鱗狀細胞癌 (HNSCC) 是一種起源於口腔、咽喉和喉部的黏膜上皮的癌症。癌細胞從初始部位擴散到周圍淋巴結是HNSCC的一個常見特徵，並且腫瘤的轉移也與患者的高死亡率相關。多項研究發現：與正常組織相比，癌細胞會重新編程其代謝以支持增加的能量需求，例如增加葡萄糖攝取率並在有氧情況下優先生成乳酸（即所謂的瓦爾堡效應）。然而，HNSCC是否因為代謝重編程而變得更具惡性和侵襲性仍不清楚。在這項研究中，我們使用了C57BL/6小鼠的頭頸癌淋巴轉移模型，分析原發性腫瘤和頸部淋巴結中轉移性腫瘤之間的差異。我們將小鼠口腔鱗狀細胞癌細胞系 (MOC2) 原位注射到小鼠舌頭。大約兩週後，將舌上的腫瘤（作為原發性腫瘤）和頸部淋巴結中的腫瘤（作為轉移性腫瘤）取下進行後續分析。首先，我們透過即時定量聚合酶連鎖反應技術(Quantitative real-time PCR service) 確認在轉移性腫瘤中，Wnt5a、Vimentin、Snai2 和 Acta2 等上皮間質轉化（epithelial-mesenchymal transition，EMT）相關的標誌物表現升高。然而，就侵襲能力（invasion ability）而言，原發性腫瘤和轉移性腫瘤之間沒有顯著差異。根據海馬生物能量分析儀（Seahorse analysis）進行的糖解壓力測試，與原發性腫瘤相比，轉移性腫瘤的細胞外酸化率 (ECAR) 明顯降低，這意味著轉移性腫瘤的瓦爾堡效應得到緩解。然而，即時定量聚合酶連鎖反應結果顯示轉移性腫瘤中的糖解相關基因表現較高。根據結果，轉移性腫瘤表現出升高的EMT和糖解相關標誌物，而細胞外酸化率則降低。這些發現顯示了HNSCC在轉移過程中的代謝重編程特徵，為進一步研究腫瘤代謝對癌症惡性和侵襲性的影響提供了新的見解，但關於代謝如何影響轉移的確切機制未來仍須更近一步的探討。 | zh_TW |
| dc.description.abstract | Head and neck squamous cell carcinoma (HNSCC) originates from the mucosal squamous epithelial cells in the head and neck region, including oral cavity, pharynx, and larynx. The spread of cancer cells from the initial site to the surrounding lymph nodes is a hallmark of HNSCC and is associated with high patient mortality. Previous studies have reported that cancer cells adapt their metabolism to meet elevated energy demands, including increased uptake of glucose and production of lactate, even under oxygen-sufficient conditions—a phenomenon known as the Warburg effect. However, whether metabolic reprogramming contributes to the lymphatic metastasis of HNSCC remains unclear. In this study, we used an HNSCC lymphatic metastasis model in C57BL/6 mice to investigate the differences between primary tumors and metastatic tumors in cervical lymph nodes. The mouse oral squamous cell carcinoma cell line (MOC2) was orthotopically injected into the tongues of mice. After approximately two weeks, the tumors from the tongue (primary tumors) and cervical lymph nodes (metastatic tumors) were harvested for subsequent analysis. Real-time RT-PCR analysis revealed that epithelial mesenchymal transition (EMT)-related markers, including Wnt5a, Vimentin, Snai2, and Acta2, were elevated in metastatic tumors. However, the Matrigel invasion assay showed no significant difference in invasion ability between primary and metastatic tumors. Additionally, glycolysis-related genes showed higher expression in metastatic tumors, as determined by real-time RT-PCR. In contrast, Seahorse analysis showed that the extracellular acidification rate (ECAR) of metastatic tumors was significantly lower than that of primary tumors, indicating an attenuation of the Warburg effect in metastatic tumors. In conclusion, these results indicate that EMT and glycolysis-related gene expression are elevated in metastatic HNSCC tumors. However, the invasion ability exhibits no significant changes, and ECAR is even decreased. These findings suggest that metastatic tumors undergo metabolic reprogramming, and the observed gene expression changes are not directly correlated with the invasive and metabolic phenotypes. Further research is required to elucidate the precise mechanisms by which metabolism influences metastasis and to determine how the expression of these genes is regulated. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-20T16:29:36Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-20T16:29:36Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 中文摘要 I
Abstract II Contents IV List of Figures VI List of Tables IX 1. Introduction 1 1.1. Head and neck squamous cell carcinoma 1 1.2. Lymph node metastasis in cancer progression 2 1.3. Cancer metabolism 5 2. Materials and Methods 9 2.1. Pathway enrichment analysis 9 2.2. Establishment of the head and neck cancer lymphatic metastasis model in mice 9 2.3. Isolation of tumor cells and primary cell culture 9 2.4. cDNA synthesis and real‐time RT‐PCR 9 2.5. Metabolic assays 10 2.6. Matrigel invasion assays 11 2.7. Transmission electron microscopy (TEM) 11 2.8. Statistical analysis 12 3. Results 13 3.1. Pathway enrichment analysis in tumors from patients with different metastatic potential 13 3.2. Establish the head and neck cancer lymphatic metastasis cell line in vivo 14 3.3. There is not significant difference in invasion ability between metastatic tumor cells and non-metastatic tumor cells in the lymphatic metastasis model 14 3.4. EMT-related gene expression is higher in metastasis tumor cells from lymphatic metastasis model 15 3.5. Expression of metabolism-related genes were upregulated in metastatic tumor cells 16 3.6. Subculturing the primary tumor in vitro does not affect the tendency of gene expression 17 3.7. Metabolic phenotypes alteration during HNSCC metastasis 17 3.8. Analysis of mitochondrial morphology by TEM showed the difference in the number of mitochondria among primary site and metastatic site 19 4. Discussion 21 5. References 26 | - |
| dc.language.iso | en | - |
| dc.subject | 代謝 | zh_TW |
| dc.subject | 頭頸癌 | zh_TW |
| dc.subject | 糖解作用 | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | 上皮間質轉化 | zh_TW |
| dc.subject | EMT | en |
| dc.subject | glycolysis | en |
| dc.subject | HNSCC | en |
| dc.subject | metastasis | en |
| dc.subject | metabolism | en |
| dc.title | 體內具轉移潛能同源口腔癌細胞系的建立與基因表達分析 | zh_TW |
| dc.title | Establishment and gene expression analysis of syngeneic oral cancer cell lines with enhanced metastatic potential in vivo | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 林能裕;陳學亭;陳家嬅 | zh_TW |
| dc.contributor.oralexamcommittee | Neng-Yu Lin;Syue-Ting Chen;Chia-Hua Chen | en |
| dc.subject.keyword | 頭頸癌,轉移,代謝,糖解作用,上皮間質轉化, | zh_TW |
| dc.subject.keyword | HNSCC,metastasis,metabolism,glycolysis,EMT, | en |
| dc.relation.page | 67 | - |
| dc.identifier.doi | 10.6342/NTU202404802 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-01-03 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | - |
| dc.date.embargo-lift | 2025-02-21 | - |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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