2013-05-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/698580摘要：結締組織生長因子為一多功能性之生長因子，其作用包括調節傷口癒合、細胞附著、細胞凋亡以及腫瘤生成等。目前，已有多種癌細胞發現有結締組織生長因子之異常表達現象。此外，結締組織生長因子也具有調控新生血管生成之功能，進而促進癌細胞轉移。近期之研究成果顯示，結締組織生長因子似乎在不同的癌症中扮演不同的角色，但在腸胃道癌症中，結締組織生長因子已被本實驗團隊發現具有檢測乃至於醫療上的潛力。本團隊最新之研究成果顯示，在胃癌細胞中直接表達結締組織生長因子或者是將癌細胞與結締組織生長因子混合後注射入免液不全小鼠體內，均可有效抑制胃癌細胞於小鼠中腹腔之轉移，並可有效延長注射胃癌細胞小鼠之壽命。此外，抑制胃癌細胞腹腔轉移可能是藉由直接與細胞表面的細胞附著因子結合後，抑制癌細胞與腸繫膜細胞之附著所達成。這些觀察強烈顯示結締組織生長因子可能是抑制腸胃道癌症腹腔轉移的重要標的。本總計劃之目的，即在於結合研究團隊為結締組織生長因子進入臨床實驗做準備。 本子計畫之研究目的有以下兩項: 1. 製備大量結締組織生長因子蛋白質片段以判斷最具治療效果之片段 2. 製備識別不同結締組織生長因子蛋白質片段之單株與多株抗體以建立靈敏之檢測系統 <br> Abstract: CTGF is a secretory protein that belongs to the CCN family (Cysteine-rich 61, CTGF and nephroblastoma-overexpressed gene (NOV)). It is a multifunctional growth factor involved in wound healing, inflammation, cell adhesion, chemotaxis, apoptosis, tumor growth, and fibrosis. Elevated CTGF expression has been detected in various tumors. Additionally, CTGF can promote angiogenesis by regulating endothelial cell growth, migration, adhesion, and survival. However, recent studies showed that over-expression of CTGF in human oral squamous cell carcinoma reduces cell growth and tumorigenecity. Similar tumor growth inhibitory effects were observed in lung cancer cells in which CTGF over-expression were less angiogenic and metastatic due to blocking of the VEGF A signaling pathway. CTGF was also reported to be a key regulator of colorectal cancer invasion and metastasis, and it appears to be a good prognostic factor. Our recent observations also suggested that CTGF may play important roles in gastric cancer. These results suggested that the expression levels of CTGF were closely associated with the survival of several GI cancers including gastric and colon origins. Our current findings demonstrated that application of CTGF, either by over-expression in the cancer cells or by ectopically applications protocols, both prevent the peritoneal metastasis of gastric and colon cancer cell lines in mice model. These inhibitory effects are likely due to a blockage of interactions between integrins molecules expressed on cancer cells and matrix proteins expressed on mesothelial cells surface. These preliminary observations strongly suggested that the application of CTGF as a potential treatment for peritoneal metastasis in these GI cancers. In this proposal, we intended to extend our understanding of the mechanisms by which CTGF prevent peritoneal metastasis. The two specific aims for this proposal are as the following: 1. We will generate different recombinant fragments of CTGF to identify the most effective domain of CTGF in preventing cancer cell adhesion to human mesothelial cell monolayer and also peritoneal metastasis in mice. 2. We will generate both mono-clonal and poly-clonal antibodies recognizing different fragments of CTGF to develop a detection system for CTGF. The successfulness of generating of these reagents will be extremely helpful for developing both treatment and also detection systems for these GI cancers.