骨肉瘤是最常見的原發性骨腫瘤，多數好發於童年和青春期，其特點為高度惡性和轉移潛能。此外有文獻證實許多癌細胞皆會有高表現量的介白素-6 (Interleukin-6; IL-6)。IL-6為具有多重免疫調節功能的細胞激素，屬於一種分泌型的細胞激素，會和IL-6R (Interleukin 6 receptor) 結合進而調控人類癌症細胞的增生、細胞凋亡、轉移及侵襲等。然而IL-6對於人類骨肉瘤移動性的機制目前不是很清楚。我們發現IL-6會促進人類骨肉瘤細胞移行能力和增加細胞間黏附因子 (Intercellular adhesion molecule-1; ICAM-1) 的表現。前處理IL-6中和性抗體、ILK抑制劑 (Kp392) 和Akt的抑制劑 (Akti) 會抑制IL-6增加人類骨肉瘤細胞移行的能力和ICAM-1的表現。在IL-6的刺激下會增加ILK及Akt磷酸化。除此之外，c-Jun抑制劑也會降低IL-6增加細胞移行能力和ICAM-1的表現。另外，IL-6也會促進c-Jun入核並結合到ICAM-1啟動子上之AP-1 element。綜合以上結果，IL-6促進ICAM-1表現經由與IL-6R的結合及ILK及Akt的訊息傳導進而活化c-Jun， 而造成人類骨肉瘤細胞株的移動性。
Osteosarcoma is the most common primary bone tumor associated with childhood and adolescence. It is characterized by high malignant and metastatic potential. Recently, some studies found that interleukin-6 (IL-6) is highly expressed in many cancer cells. However, the effects of IL-6 on cell motility and intercellular adhesion molecule-1 (ICAM-1) expression in human osteosarcoma cells are rarely known. Here we found that IL-6 induced the cell motility and expression of ICAM-1 in human osteosarcoma cells. IL-6R monoclonal antibody (mAb), integrin-linked kinase inhibitor (Kp392) and Akt inhibitor inhibited IL-6-induced cell mobility and ICAM-1 expression. IL-6 stimulation increased the phosphorylation of ILK and Akt. In addition, c-Jun inhibitor (curcumin and tanshinone-IIA) also antagonized IL-6 increased cell motility and ICAM-1 expression. Moreover, IL-6 induced the binding of c-Jun to the AP-1 element on the ICAM-1 promoter. Taken together, our results suggested that IL-6 enhances motility of osteosarcoma cells by increasing ICAM-1 expression through the IL-6R, ILK, Akt, and AP-1 signal transduction pathway.
