Elucidation of molecular mechanism of resistance to chemoradiotherapy of esophageal cancer and development of new treatment focusing on cancer stem cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: KIMURA yasue 九州大学, 医学研究院, 共同研究員 (70631927)
• Co-Investigator(Kenkyū-buntansha): 沖 英次 九州大学, 大学病院, 講師 (70380392) ; 佐伯 浩司 九州大学, 大学病院, 講師 (80325448) ; 中島 雄一郎 九州大学, 医学研究院, 助教 (40733564)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 食道扁平上皮癌 / がん幹細胞 / CD44v9

Outline of Final Research Achievements

CD44v9 levels were higher at the tumor invasive front compared with the center of the tumor and were higher in metastatic lymph nodes compared with primary tumors. High levels of CD44v9 at the tumor invasive front were significantly associated with deeper tumor invasion, and shorter overall survival and recurrence-free survival. The expression of CD44v9 was increased by transforming growth factor-β treatment, which induced esophageal squamous cell carcinoma cells to undergo the epithelial-mesenchymal transition. Moreover, inhibition of CD44v9 expression decreased the migration and invasiveness of esophageal squamous cell carcinoma cells. These results indicate that the expression of CD44v9 at the tumor invasive front was strongly associated with the epithelial-mesenchymal transition and poor prognosis of patients with esophageal squamous cell carcinoma.

Free Research Field

消化器外科、腫瘍外科

Academic Significance and Societal Importance of the Research Achievements

CD44のバリアントアイソフォーム(CD44v)の発現は、遠隔転移と関連していることが報告されており、がん幹細胞のマーカーの一つと考えられていた。
食道扁平上皮癌におけるCD44v9の発現と臨床病理学的因子および転移獲得能に関与するか明らかにした。CD44v9の高発現症例は深達度が深く、予後不良であった。食道扁平上皮癌深部浸潤部のEMTに伴い発現が誘導され、腫瘍細胞の遊走能・浸潤能が亢進し、悪性度獲得に寄与すると考えられた。以上から、本研究において、CD44v9の発現は食道扁平上皮癌における予後不良因子のバイオマーカーとなり、治療標的因子となりえることが示唆された。