https://scholars.lib.ntu.edu.tw/handle/123456789/192332
標題: | 醣化酵素在老鼠胰臟癌細胞轉移至肝臟的角色 | 作者: | 田郁文 | 關鍵字: | angiogenesis;Intravasation;metastasis | 公開日期: | 31-七月-2005 | 出版社: | 臺北市:國立臺灣大學醫學院外科 | 摘要: | 新生血管的形成對於腫瘤的成長是必要的,而且在我們之前的實驗裏發現「與腫瘤細 胞進入血管這一轉移步驟」唯一有關的因子也是新生血管的形成。原發腫瘤會分泌許 多血管生成促進因子使血管內膜細胞增生,增生的內膜細胞為了能長進腫瘤會分泌細胞間 質金屬蛋白脢來消化腫瘤間質。在這過程中早期的腫瘤細胞是極可能被動地被包進血管 內腔而轉移出去。Hoglund 他們藉由microarray 的方法觀察到存在於在臨床上無遠處器 官轉移的病人的骨髓的腫瘤細胞是屬於腫瘤發育史上早期的細胞。由於這些潛伏的腫瘤 細胞擁有相當少的染色體變異,因此極可能是來自早期的腫瘤,到了目標器官後由於懷環 境(土壤)的改變,因此進一步的細胞基因的突變變緩慢而停滯在冬眠狀態。 腫瘤在冬眠時由於無新生血管的形成因而無法獲得足夠的氧氣與養分,因此我們推論 潛伏在肝臟的腫瘤細胞如果有較多的醣分解(glycolysis)酵素會有較大的機會在無氧而有大 量肝醣(glycogen)存在的肝臟存活下來,也應該會較容易長成轉移病灶。為了證實這個推 論,我們預備把老鼠醣化酵素(enolase α)基因轉殖到胰臟腫瘤細胞測試這些強烈表現醣化酵 素的腫瘤細胞是否更容易造成肝臟轉移。 Angiogenesis is essential for the growth of primary tumor and, as shown in our previous studies , is also the only significant intravasation-related metastatic factor. Tumor’ll secrete or induce many angiogenic factors to induce neovascularizatioin. Endothelial cells stimulated by these angiogenic factors such as vascular endothelial growth factor, secrete matrix metalloproteinase-2 (Gelatinase A) which contributes to degradation of basement membrane in microvessel walls. This breakdown in the vascular basement membrane may facilitate the extravasation of endothelial cells during formation of neovascularization sprouts, as well as intravasation of tumor cells into lumen. If tumor vessel formation is rapid and haphazard and endothelial proliferation is insufficient or endothelial junctions are unstable, cancer cells may be exposed to the lumen and passively enter the circulation during the angiogenic process. Thus, in contrast to the present view “metastasis marks the end in a sequence of genomic changes underlying the progression of an epithelial cell to a lethal cancer”, these results imply that tumor cells may passively enter the circulation early during multistep tumorigenesis. From the synoptic analysis of cytogenetic data from thousands of solid tumors, it was deduced that the number of cytogenetic imbalances per tumor reflects to some extent the biological age of the tumor. Hence, the relative small number of chromosomal aberrations in many latent disseminated cells suggests they left the primary site early and the further accumulation of imbalances may have been decelerated, perhaps by environmental constraints, which leads to the tumor dormancy. Results of our studies, tumor dormancy, and cancer of unknown primary syndromes all stress the importance of soil to develop established metastatic growth. Thus, we’re going to focus further studies on metastatic steps after extravasation. As previous described, tumor depends on angiogenesis to sustained growth. Once the tumor mass reaches a diameter of ~2 mm, establishment of new vascular system is essential for its survival. Until then, endurance in hypoxic condition is essential for its survival. In liver, there is a plenty storage of glycogen and these glycogen can be used as substrate of glycolysis in an anoxic condition. Theoretically, tumor cells with enzymes for glycolysis (such as enolase α) may have a 3 greater chance to survive in liver and remained in dormant state. To test this hypothesis, we’ll try to increase the liver metastasis by injecting murine-enolase-overexpressing pancreatic cancer cells. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/24563 | 其他識別: | 932314B002272 | Rights: | 國立臺灣大學醫學院外科 |
顯示於: | 醫學系 |
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932314B002272.pdf | 191.4 kB | Adobe PDF | 檢視/開啟 |
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