2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649322摘要：胎盤生長因子，一種糖基化的同二聚體蛋白質，和血管內皮生長因子有53% 同質性，與血管內皮生長因子接受器Flt-1 結合，具有調控血管內皮生長因子活性的功能。缺少胎盤生長因子對於正常胚胎形成及血管發育有不可忽略的作用，但胎盤生長因子也表現於血管增生之腎細胞癌，及某些甲狀腺與生殖細胞腫瘤中。由體外實驗證明胎盤生長因子的過度表現會造成腫瘤生長及血管形成，並誘導生存基因的表現，及抑制細胞凋亡。胎盤生長因子已知與許多固著性腫瘤的進展有關連，這些關連性起初都相信是胎盤生長因子誘導血管形成的結果。而最近幾年的研究已開始證明，胎盤生長因子可能是直接作用於腫瘤細胞上。因為胎盤生長因子的表現濃度在許多腫瘤上都比非腫瘤區還要高，並且具有統計學上的意義，例如：乳癌、肺癌、大腸直腸癌及胃癌等，外源性之胎盤生長因子會直接刺激腫瘤細胞，例如乳癌細胞之致死性及侵略性，而與病人的存活率相關，但是直接作用於癌細胞的機轉仍然不明確。然而胎盤生長因子與血管形成，腫瘤轉移，及預後在口腔癌中卻未見報告，口腔癌組織中的胎盤生長因子、接受器Flt-1 之表現尚未見於任何文獻報告。我們最近利用胎盤生長因子抗體對口腔癌檢體以免疫染色法做的發現有胎盤生長因子過度表現，正常口腔組織則無表現，先導研究亦發現多種口腔癌細胞株均表現胎盤生長因子mRNA。所以，提出本三年計劃擬於三年內逐步深入探討口腔癌之胎盤生長因子過度表現是否可以做為口腔癌致癌危險性評估，診斷，預後價值指標，癌化的角色及機轉。並在in vitro 及in vivo 模式探索抑制胎盤生長因子作用，做為未來口腔癌治療的可行性及其作用機轉。提供發展未來口腔癌治療新策略之參考。<br> Abstract: Placenta growth factor (PlGF), a dimeric glycoprotein with 53% homology to VEGF,binds to VEGF receptor-1, may function by modulating VEGF activity. Absence of PlGF hada negligible effect on vascular development and normal embryogenesis. PlGF expression hasbeen reported in hypervascular renal cell carcinomas and in some thyroid and germ celltumours. Overexpression of PlGF leads to tumour growth as well as vascular formation,induces expression of survival genes, and inhibits apoptosis in vitro. PlGF has beenimplicated in the progression of a number of solid tumours. This involvement was initiallybelieved to be the results of induction of angiogenesis by PlGF. However, in recent years,evidence began to indicate that PlGF may directly act on cancer cells. PlGF protein level issignificantly higher in many tumours compared with non-tumour foci, such as breast cancer,lung cancer, colorectal cancer and gastric cancer and is correlated with patient’s survival.Recent in vitro and in vivo studies have shown that exogenous PlGF have a directstimulatory effect on cancer cells, such as the motility and invasion of breast cancer cell.However, the correlations between PlGF, angiogenesis, metastasis, and prognosis in coloncancer are not clear. The goal of our study was to evaluate correlations among these factors.The expression of PlGF or Flt-1(receptor of PlGF) in oral cancer is not yet published in theliteratures. Recently, the preliminary data were shown that overexpression of PlGF wasdetected by immunohistochemistry with contrast to low expression in the normal specimen.Also, RT-PCR technique was used to find the overexpression of mRNA in oral cancer celllines as well. So we proposed the consecutive 3-year study to collect surgical specimen, bloodand saliva, and study on the carcinogenesis of PlGF using cancer cell lines and an animalmodel in oral cancer, and chemopreventive possibility for the treatment of oral cancer usingPlGF inhibitor.胎盤生長因子血管內皮生長因子免疫化學染色法口腔癌細胞株Placental Growth Factor (PlGF)Vascular Endothelial Growth Factor (VEGF)ImmunohistochemistryOral cancer cell lines