2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647364摘要：癌症轉移為⼤大多數癌症病患死亡之主因。︒｡過去數⼗十年來不論是臨床研究學者或是基礎研究學者均致⼒力於此機轉之分⼦子與細胞層級研究。︒｡關於腫瘤微環境 (microenvironment) 所扮演的⾓角⾊色，如癌旁纖維母細 (cancer associated fibroblasts, CAFs)，腫瘤相關巨噬細胞 (tumor associated macrophages)，內⽪皮細胞 (endothelial cells) 等也都多有著墨。︒｡然⽽而有關於癌症轉移的初始階段 (initiation) 卻少有探討。︒｡因此本研究想透過觀察癌旁纖維母細胞在癌症轉移的異種細胞遷移 (coordinated migration) 中所扮演的調節⾓角⾊色，來進⼀一步的瞭解癌症轉移起始階段之機轉，以期能開啟早期癌轉移之預防治療與積極治療。︒｡在此我們透過建⽴立⼀一 3-D 共同細胞培養系統來模擬癌細胞與癌旁纖維母細胞在體內交互作⽤用之模式。︒｡希望透過三年期的計畫來深⼊入了解癌轉移的初始階段中癌細胞與癌旁纖維母細胞的共同遷移：⽬目標⼀一：建⽴立⼀一新穎 3-D 共同細胞培養系統⽬目標⼆二：研究癌旁纖維母細胞與癌細胞間之交互作⽤用⽬目標三：探討癌旁纖維母細胞與癌細胞間之直接接觸之影響⽬目標四：了解癌旁纖維母細胞與癌細胞間的異種細胞共同遷移在癌轉移扮演之⾓角⾊色⽬目標五：分析不同階段之癌旁纖維母細胞之臨床意義<br> Abstract: Metastasis is the leading reason for the resultant mortality of patients with cancer. The past fewdecades have witnessed remarkable progress in understanding the molecular and cellular basis of thislethal process in cancer. The unique roles of microenvironment are also been studied, includingcancer associated fibroblasts (CAF), tumor associated macrophages, and endothelial cells. However,the initiation step of metastasis processes is still unknown. In this study, we propose to investigatethe roles of coordinated migration regulated by CAF in the initiation stage of metastasis. We aim atproposing a new therapeutic concept in the prophylactic treatment and advanced treatment in tumormetastasis. We established a novel 3-D co-culture system to study the interaction between cancerand CAF. We are proposing a series of three-year interventions to study the roles of CAFs in theinitiation stage of cancer metastasis via the coordinated migration and the direction of movement. Itmay also imply that the interaction between cancer cells and CAFs might be a novel treatmentstrategy in cancer metastasis by targeting the direct contact interaction between cancer cells andCAFs.Aim 1. Establishment of the novel 3-D co-culture systemAim 2. Investigation of the systemic structure formed by CAF and cancer cellsAim 3. Investigation of heterosynapse upon stromal-epithelial interactionAim 4. Investigation of the roles of coordinated migration guided by CAF in metastasisAim 5. Investigation of clinical significance腫瘤微環境癌轉移癌旁纖維母細胞共同遷移Tumor microenvironmentMetastasisCancer associated fibroblasts (CAFs)Coordinated migration