細胞増殖因子からみた癌細胞と間質細胞との相互作用 -その分子機構-

• 研究課題/領域番号: 06281113
• 研究種目: 重点領域研究
• 配分区分: 補助金
• 研究機関: 広島大学
• 研究代表者: 田原 榮一 広島大学, 医学部, 教授 (00033986)
• 研究分担者: 井出 利憲 広島大学, 医学部, 教授 (60012746) ; 清水 信義 慶応義塾大学, 医学部, 教授 (50162706) ; 河野 通明 岐阜薬科大学, 薬学部, 助教授 (00027335) ; 松本 邦夫 大阪大学, 医学部, 助手 (90201780) ; 駒田 雅之 関西医科大学, 医学部, 助手 (10225568)
• 研究期間 (年度): 1994
• 研究課題ステータス: 完了 (1994年度)
• 配分額: 17,500千円 (直接経費: 17,500千円); 1994年度: 17,500千円 (直接経費: 17,500千円)
• キーワード: 増殖因子 / 増殖因子レセプター / 癌と間質との相互作用 / シグナル伝達 / HGF / c-met / p115

研究概要

HGFは正常組織では主に間質細胞によって産生・分泌されるが、種々のヒト悪性腫瘍(グリオーマ、肺小細胞癌、胃癌、大腸癌、食道癌など)ではHGF転写の多様性オートクリンループが存在し、癌細胞の遊走・浸潤促進に重要な役割を演ずることが示された。HGFのtwo-kringle variantに加えて、本年度ではHGF light chainのみをコードする新しいHGF異常転写産物が胃癌培養株HSC-39で発現していることが見いだされ、現在その機能について解析中である。またHGF誘導因子として、IL-1-alpha,IL-1-betaのみならず、PDGF,FGF(aFGF,bFGF)などの増殖因子も含まれることが明らかにされ、これらサイトカインと増殖因子がHGF/c-met系を介しての癌細胞-間質細胞相互作用を惹起させ、癌の悪性化に関与する可能性が示唆された。そして、本年度最も興味ある点は、HGF,EGF,PDGFなどの増殖因子によってチロシン・リン酸化されるp115の構造が明らかにされ、p115は増殖因子のシグナル伝達に普遍的な、そしてユニークな役割を果たす因子であることが示唆された。

研究成果

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