Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells

Cancer Genomics Proteomics. 2016;13(6):437-442. doi: 10.21873/cgp.20006.

Abstract

Background: 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.

Materials and methods: Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells.

Results: 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).

Conclusion: The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells.

Keywords: Metastasis; differential gene expression; lymphoma; phospholipase D.

MeSH terms

  • Animals
  • CCN Intercellular Signaling Proteins / biosynthesis*
  • CCN Intercellular Signaling Proteins / genetics
  • Cell Line, Tumor
  • Cystatins / biosynthesis
  • Cystatins / genetics
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics*
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics
  • Humans
  • Lymphoma / genetics*
  • Lymphoma / pathology
  • Mice
  • Microarray Analysis*
  • Neoplasm Metastasis
  • Phospholipase D / biosynthesis
  • Phospholipase D / genetics
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • RNA, Messenger / biosynthesis
  • Signal Transduction / genetics
  • Suppressor of Cytokine Signaling Proteins / biosynthesis
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • CCN Intercellular Signaling Proteins
  • CCN4 protein, mouse
  • Cystatins
  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Rhox5 protein, mouse
  • Socs2 protein, mouse
  • Suppressor of Cytokine Signaling Proteins
  • Transcription Factors
  • cystatin F, mouse
  • phospholipase D2
  • Phospholipase D