Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.
Int J Biol Sci. 2012;8(3):383-93. doi: 10.7150/ijbs.3579. Epub 2012 Feb 23.
Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates both in tumor stroma and cancer cells and is highly regulated by various cytokines. The aberrant expression of versican and its isoforms is known to modulate cell proliferation, differentiation, and migration, all of which are features of the invasion and metastasis of cancer; versican is also known to favour the homeostasis of the ECM. Interleukin-11 (IL-11) is an important cytokine that exhibits a wide variety of biological effects in gastric cancer development. Here, we analysed the expression of versican isoforms and found that the major isoforms expressed by both gastric carcinoma tissue and gastric cell lines were V0 and V1, and V1 was significantly higher in gastric carcinoma tissue. The treatment of the gastric cell lines AGS and MKN45 with rhIL-11 resulted in a significant increase in the expression of V0 and V1. Exogenous IL-11 increased migration in AGS and MKN45 cells, whereas these effects were reversed when the expression of V0 and V1 were abolished by siRNA targeting versican V0/V1. Collectively, these findings suggest that the abnormally expressed versican and its isoforms participate, at least in part, in the progress of gastric carcinoma triggered by IL-11.
神经黏连蛋白聚糖是细胞外基质（ECM）的一种普遍成分，在肿瘤基质和癌细胞中均有积累，并且受到各种细胞因子的高度调节。神经黏连蛋白聚糖及其异构体的异常表达已知可调节细胞增殖、分化和迁移，所有这些都是癌症侵袭和转移的特征；神经黏连蛋白聚糖也有利于 ECM 的动态平衡。白细胞介素-11 (IL-11) 是一种重要的细胞因子，在胃癌发展中表现出广泛的生物学效应。在这里，我们分析了神经黏连蛋白聚糖异构体的表达，发现胃癌组织和胃细胞系中表达的主要异构体是 V0 和 V1，并且 V1 在胃癌组织中明显更高。rhIL-11 处理胃细胞系 AGS 和 MKN45 导致 V0 和 V1 的表达显著增加。外源性 IL-11 增加了 AGS 和 MKN45 细胞的迁移，而当通过靶向神经黏连蛋白聚糖 V0/V1 的 siRNA 消除 V0 和 V1 的表达时，这些作用被逆转。总之，这些发现表明异常表达的神经黏连蛋白聚糖及其异构体至少部分参与了由 IL-11 触发的胃癌进展。
