Chahal Manpreet S, Ku H Teresa, Zhang Zhihong, Legaspi Christian M, Luo Angela, Hopkins Mandi M, Meier Kathryn E
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A.
Division of Development & Translational Diabetes and Endocrine Research, Beckman Research Institute of City of Hope, Duarte, CA, U.S.A.
Cancer Genomics Proteomics. 2016;13(6):437-442. doi: 10.21873/cgp.20006.
Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis.
Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells.
Many differences were observed between non-metastatic and metastatic cell lines. One of the most striking new findings was up-regulation of mRNA for the matricellular protein WNT1-inducible signaling pathway protein 1 (CCN4) in metastatic cells; increased protein expression was verified by immunoblotting and immunocytochemistry. Other differentially expressed genes included those for reproductive homeobox 5 (Rhox5; increased in metastatic) and cystatin 7 (Cst7; decreased in metastatic). Differences between PLD2-expressing and parental cell lines were limited but included the signaling proteins Ras guanyl releasing protein 1 (RGS18; increased with PLD2) and suppressor of cytokine signaling 2 (SOCS2; decreased with PLD2).
The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells.
先前的研究对EL4小鼠淋巴瘤细胞系的变体进行了特征描述。在同基因小鼠中，一些变体不具有转移性，而其他变体具有转移性。此外，用磷脂酶D2（PLD2）稳定转染具有转移性的EL4细胞，可进一步增强其转移性。
对不具有转移性、具有转移性以及表达PLD2的具有转移性的EL4细胞进行mRNA表达的微阵列分析。
在不具有转移性和具有转移性的细胞系之间观察到许多差异。最显著的新发现之一是，在具有转移性的细胞中，基质细胞蛋白WNT1诱导信号通路蛋白1（CCN4）的mRNA上调；通过免疫印迹和免疫细胞化学证实了蛋白表达增加。其他差异表达的基因包括生殖同源盒5（Rhox5；在具有转移性的细胞中增加）和胱抑素7（Cst7；在具有转移性的细胞中减少）。表达PLD2的细胞系与亲本细胞系之间的差异有限，但包括信号蛋白Ras鸟苷释放蛋白1（RGS18；随PLD2增加）和细胞因子信号转导抑制因子2（SOCS2；随PLD2减少）。
这些结果为可能参与赋予淋巴瘤细胞转移能力的信号通路提供了见解。
