Role of FGF-2 in interaction of oral squamous cell carcinoma cells and fibroblasts in an in vitro invasion system

癌細胞が浸潤・増殖する際に宿主反応として間質線維化を伴い, 増殖した線維芽細胞との相互作用を介して癌細胞は活性化すると考えられているが, 詳細については不明である。本研究では, 浸潤先進部の癌細胞で過剰発現するFGF-2が線維芽細胞の増殖および癌細胞の浸潤・増殖に与える影響についてin vitroで検討した。癌浸潤様式の異なる3種類のヒトロ腔扁平上皮癌細胞株 (OSC-20: 3型, OSC-19: 4C型, HOC313: 4D型) の培養上清により, ヒト正常歯肉線維芽細胞 (HGF-1細胞) の増殖は促進された。特に, HOC313細胞の培養上清で顕著な増殖促進効果を示し, OSC-20細胞, OSG19細胞に比べて強いFGF-2の発現を認めた。また, Recombinant Human FGFL2 (50ng/ml) により線維芽細胞の増殖のみならず, 各癌細胞の浸潤・増殖も促進され, controlと比較するとOSC-19細胞, HOC313細胞で有意差を認めた (p<0.05) 。in vitro浸潤モデルにおいてFGF-2中和抗体 (2μg/ml) を添加すると, OSC-20細胞, OSC-19細胞は浸潤抑制を示した。以上の結果より, 高度浸潤性の扁平上皮癌細胞ほど多くのFGF-2を産生し, autocrineに作用して浸潤・増殖を促進する一方, paracrineにも作用することで線維芽細胞の増殖を促進することにより癌細胞の浸潤・増殖活性に関与している可能性が示唆された。

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