| 摘要: | WISP-1 (Wnt-induced secreted protein-1)是CCN family (Cyr61-CTGF-Nov family) 中的一員，它又可以稱為CCN4。CCN家族可以進行各種生理的調控如：細胞生長、細胞貼附能力、促進細胞移動及刺激細胞增生作用等。而WISP-1可以透過與細胞表面的integrin結合進而促進細胞貼附或移行能力，然而WISP-1與軟骨肉瘤的移行並不明朗。本實驗中我們發現WISP-1可以透過α5β1 integrin接受器增加人類軟骨肉瘤細胞(JJ012細胞)的移行和matrix metalloproteinase (MMP)-2的表現。我們使用α5β1單株抗體可以有效地抑制WISP-1誘導細胞移行能力和MMP-2的產生。給予WISP-1後也會促進FAK、MEK、ERK、IKKα/β、IκBα及p65的活化；使用FAK、MEK、ERK、IKKα/β、IκBα和NF-κB專一性訊息傳遞抑制劑，都會抑制WISP-1增加人類軟骨肉瘤細胞的移行能力與MMP-2的產生。細胞轉染FAK siRNA、 FAK、MEK、ERK、IKKα和IKKβ mutant、MMP-2 siRNA及WISP-1 shRNA也可以有效降低WISP-1促使癌症細胞的轉移。由我們的實驗結果指出WISP-1會經過α5β1 integrin 接受器調控人類軟骨肉瘤細胞的移行能力與MMP-2的表現，是透過FAK/MEK/ERK/IKKα/β/NF-κB路徑。
關鍵字：WISP-1、細胞黏著受體、人類軟骨肉瘤細胞、移行。
WISP-1 (Wnt-induced secreted protein-1), from the CCN gene family, also call CCN4, which is involved in many cellular activities such as growth, differentiation, cell motility, adhesion and division. Previously study display WISP-1 can induces cell adhesion and cell motility via cellular surface integrin. However, the effect of WISP-1 on migration activity in human chandrosarcoma cells is mostly unknown. Here, we found that WISP-1 increased the migration and expression of matrix metalloproteinase (MMP)-2 through the α5β1 integrin receptor in human chondrosarcoma cells (JJ012 cells). α5β1 monoclonal antibody inhibited WISP-1-induced increase migration and MMP-2 expression. Activations of focal adhesion kinase (FAK), MAPK kinase (MEK), extracellular signal-regulated kinase (ERK)﹐IκB kinase α/β (IKK α/β), IκBα and NF-κB pathways after WISP-1 treatment were demonstrated, and WISP-1-induced expression of MMP-2 and migration activity were inhibited by the specific inhibitor of FAK, MEK﹐ERK﹐IKK α/β﹐IκBα and NF-κB cascades. Transfection of cells with FAK, MEK, ERK, IKKα and IKKβ mutant also reduced WISP-1-mediated cancer migration. Taken together, our results suggest that WISP-1 acts through FAK/MEK/ERK/ IKKα/β, which in turn activates NF-κB, resulting in the activation of MMP-2 and contributing to the migration of human chondrosarcoma cells.
Key world：WISP-1、Integrin、Chondrosarcoma cells、Migration. |
