多形性膠質母細胞瘤(glioblastoma multiforme, GBM)是死亡率最高的腦腫瘤其特質具有高度發炎反應，易被小膠質細胞(microglia)浸潤且被各種促發炎因子環繞。細胞因子(cytokine)大量存在於腫瘤微環境中並且參與腫瘤的發展及惡性程度。已知細胞黏附分子(adhesion molecules)介導細胞間的相互作用，特別是在免疫細胞及目標組織。細胞間黏附分子(Intercellular adhesion molecule, ICAM)-1也稱為CD54及血管細胞黏附分子(Vascular cell adhesion protein, VCAM)-1也稱為CD106已被確認為腦內皮細胞主要的adhesion molecules，其促進腦中白細胞(leukocytes)附著和滲透。然而cytokines和adhesion molecules在單核細胞(monocyte)和巨噬細胞(macrophage)黏附到GBM上的作用大多是未知的。在這項研究中，發現到interleukin(IL)-1β隨著濃度增加或時間增加的方式誘導ICAM-1和VCAM-1蛋白質表現。此外，IL-1β濃度上升或時間增加也會誘導ICAM-1和VCAM-1信使核醣核酸(messenger ribonucleic acid, mRNA)表現。另外，為了確認IL-β是否誘導ICAM-1及VCAM-1的表達並促使monocytes接附到GBM。首先使用單核細胞結合測試(monocytes binding assay)進一步確認monocytes結合GBM的能力，並用IL-β以濃度梯度的方式處理GBM增加了THP-1 monocytes的黏附。並且用小分子干擾核糖核酸(small interfering ribonucleic acid, siRNA)細胞轉染(transfection)降低ICAM-1及VCAM-1在GBM中的表達，並且也減少了IL-β誘導增加的monocytes結合GBM的能力。總之，這些結果表明IL-β誘導的ICAM-1及VCAM-1表達是monocytes與GBM結合的重要調節因子。
Glioblastoma (GBM) is the most lethal brain tumor with highly inflammation in nature, infiltrated by microglia and surrounded by various pro-inflammatory cytokines. Cytokines are abundant in tumor microenvironment and involved in tumor progression. Adhesion molecules are known to mediate cell-cell interactions, particularly between immune cells and target tissues. ICAM-1 (also known as CD54) and VCAM-1 (also known as CD106) have been recognized as the major adhesion molecules of brain endothelial cells that facilitate attachment and penetration of leukocytes in the brain. However, the role of cytokines and adhesion molecules in monocyte/macrophage adhesion to human GBM is mostly unknown. In this study, we found that interleukin (IL)-1β induced ICAM-1 and VCAM-1 protein expression in a dose-dependent and time-dependent manner. In addition, IL-1β also induced ICAM-1 and VCAM-1 mRNA expression in a dose-dependent and time-dependent manner. Moreover, we also determined whether IL-1β induces ICAM and VCAM-1 expression and promotes human monocyte adhesion to GBM. The ability of monocytes to bind to GBM was determined using the monocyte-binding assay. Treatment of GBM with IL-1β increased THP-1 monocyte adhesion in a dose-dependent manner. Transfection with siRNA against ICAM-1 or VCAM-1 significantly decreased the expression of ICAM-1 and VCAM-1, and abolished the IL-1β-enhanced monocyte adhesion to GBM. Taken together, these results indicated that IL-1β-induced ICAM-1 and VCAM-1 expression are importantly modulators of adhesion of monocytes with GBM.
