Part I:長久以來CXCR4被認為是趨化激素CXCL12唯一的接受體，並藉由彼此間的相互作用調控腫瘤的生長及轉移。最近，已有許多文獻證實CXCL12有另一個接受體稱為CXCR7，又稱RDC1。此次研究主要探討CXCL12是否參與調控口腔癌細胞的增生及轉移。利用免疫組織化學染色法檢測112個病人組織切片，發現CXCL12陽性比例為59%及CXCR4、CXCR7陽性比例為80%。同時檢測23個轉移至周邊淋巴結的口腔癌組織切片，發現CXCL12陽性比例為52%，而CXCR4及CXCR7為百分百表達。接著利用西方墨點法及流式細胞儀檢測七株口腔癌細胞株表達CXCL12、CXCR4及CXCR7蛋白的情形，其中有六株細胞表達CXCL12、三株細胞表達CXCR7以及七株細胞皆表達CXCR4。CXCL12可促進口腔癌細胞的增生作用，並且添加CXCR4及CXCR7抗體則可抑制癌細胞增生。藉由以上結果得知，CXCL12透過CXCR4及CXCR7促進口腔癌細胞的增生作用。
Part II:Cyr61為CCN蛋白家族的成員，為一分泌型蛋白並與細胞外基質結合。此蛋白主要參與調控細胞的生長及分化作用，而決多數的CCN蛋白成員可調控各種腫瘤細胞的移動性、細胞分裂以及細胞的黏附性。然而，Cyr61是否與口腔癌細胞相關性目前不清楚，因此，此次研究主要探討Cyr61是否與口腔癌細胞有關。首先我們利用免疫組織化學染色方法檢測一百個口腔癌患者組織切片，並且發現Cyr61高度表達於口腔癌組織切片中，並且也發現在同一口腔癌組織切片中可觀察到Cyr61會隨著口腔癌癌化的程度而有明顯的表達情形，因此藉由以上結果可知Cyr61與口腔癌的進程有其相關性。
Part I:Chemokine CXCL12（SDF-1） was thought to act through its “canonical” receptor, CXCR4, to promote the growth of primary tumors and progression to metastatic disease in many cancers. Recently, several reports have documented that CXCR7/RDC1 also plays as a chemokine receptor for CXCL12. So we want to investigate the potential role of CXCL12 and the responsive receptor in OSCC. From examining 112 primary cancer specimens of OSCC patients by immunohistochemistry staining, we found that 59% cases expressed chemokine CXCL12, 80% cases expressed CXCR4 and 87％ cases expressed CXCR7. In all of the 23 metastatic lymph nodes the metastatic oral cancer cells expressed both CXCR4 and CXCR7 receptors, and 52% cases expressed chemokine CXCL12. From exploring seven OSCC cell lines by western blot and flow cytomestry, six cell lines expressed chemokine CXCL12, three cell lines expressed receptor CXCR7, and all of the seven cell lines expressed CXCR4. Furthermore, CXCL12 can stimulate oral cancer cell proliferation under serum starvation condition. And the CXCL12-induced proliferation effect can be blocked by addition of CXCR4 or CXCR7 antibodies. We concluded that CXCL12 mediates the cellular proliferation in the progression of OSCC through both CXCR4 and CXCR7 receptors.
Part II:Cysteine-rich 61 (Cyr61), one of the CCN gene family, is a secreted and matrix-associated protein. It is involved in many cellular activities such as growth and differentiation. Most of CCN family membranes can regulate the cell motility, division and adhesion in various cancer by interaction of integrin. However, the effect of Cyr61 on progression in human oral squamous cell carcinoma (OSCC) is mostly unknown. Here, we investigated the role of Cyr61 in the progression of OSCC. From examining 100 primary cancer specimens of OSCC patients by immuohistochemistry staining, we found that Cyr61 highly expressed in OSCC specimens. We suggest that Cyr61 have significant correlations with the progression of oral squamous cell carcinoma.
