血管內皮生長因子對口腔癌幹細胞之影響

口腔癌是台灣男性常見的癌症之一。初期口腔癌的治療方式以手術為主，但對於末期患者而言，手術治療不僅造成顏面外觀及咀嚼功能極大的缺陷，其五年存活率也只有30~50%，因此新的抗癌藥物仍持續在研發中。Genetech 公司所研發之標靶治療藥物Bevacizumab (Avastin)為針對血管內皮生長因子(Vascular endothelial growth factor, VEGF)之單株抗體藥物，其在治療轉移性大腸直腸癌具有療效。此外，血管內皮生長因子也被證實對口腔癌細胞有直接作用，使其經由上皮-間質轉化而進行侵犯及轉移。然而，在臨床治療方面，第二期臨床試驗的成果顯示並不優於傳統化學治療藥物。因此血管內皮生長因子對頭頸癌細胞的影響仍須進一步探討。最近的研究發現，血管內皮生長因子能製造適合癌幹細胞的微環境，對癌幹細胞有促進作用。本實驗以群落形成試驗分離出SAS細胞株之次族群，並經過表面抗原檢測顯示次族群中具有較多的CD44陽性細胞，同時表現較接近間質細胞的性狀。而細胞侵犯試驗證實了次族群細胞確實具有較強的侵犯能力，且加入血管內皮生長因子抗體中和後，次族群的侵犯能力明顯被抑制。因此相較於對原始細胞族群使用抗體，針對次族群使用抗體的效果更為顯著，因此，設計用血管內皮生長因子單株抗體以口腔癌幹細胞作為標靶的治療策略，或許能提供更有效的治療。

關鍵字

血管內皮生長因子；癌幹細胞

並列摘要

Oral cancer in men is one of the most prevalent malignancies in Taiwan. For the patient with advanced disease, poor prognosis and the problem of esthetic and functions makes the treatment to be a large challenge. Bevacizumab (AvastinR), an anti-VEGF (Vascular endothelial growth factor) monoclonal antibody drug, is proved to be effective on treating metastatic colorectal cancer. In addition, VEGF mediated epithelia-mesenchymal transition, which induces invasion and metastasis of oral cancer cells is also reported. However, trials using Bevacizumab for the treatment of oral cancer was not effective. Thus, more investigations are needed. Recently, VEGF was found regulates a niche that benefits the cancer stem cells. The objective of this study is to investigate the effect of monoclonal anti-VEGF antibody on oral cancer stem cells. SAS cell line (poorly differentiated tongue squamous cell carcinoma from human) was used, and a subgroup was isolated with colony forming assay. The results showed that the CD44 positive subgroup cells presented more mesenchymal phenotype and had more invasive abilities in an invasion assay. The anti-VEGF antibody inhibited the mesenchymal phenotype expression and suppressed invasive ability. The results suggest that targeting the anti-VEGF antibody on oral cancer stem cells would be a more effective treatment strategy.

並列關鍵字

Vascular endothelial growth factor ； Cancer stem cells

參考文獻

(1) Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002: 2: 795-803.

(2) Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989: 161: 851-858.

(3) Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004: 25: 581-611.

(6) Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993: 362: 841-844.

(7) Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992: 267: 26031-26037.

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血管內皮生長因子對口腔癌幹細胞之影響

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