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


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).


CONCLUSIONS
The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells.
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A.
Manpreet S
MS
Chahal
Division of Development & Translational Diabetes and Endocrine Research, Beckman Research Institute of City of Hope, Duarte, CA, U.S.A.
H Teresa
HT
Ku
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A.
Zhihong
Z
Zhang
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A.
Christian M
CM
Legaspi
Division of Development & Translational Diabetes and Endocrine Research, Beckman Research Institute of City of Hope, Duarte, CA, U.S.A.
Angela
A
Luo
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A.
Mandi M
MM
Hopkins
Department of Translational Research and Cellular Therapeutics, College of Pharmacy, Washington State University, Spokane, WA, U.S.A. kmeier@wsu.edu.
Kathryn E
KE
Meier
D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015891:Cystatins / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D046228:Microarray Analysis; D009362:Neoplasm Metastasis; D010739:Phospholipase D / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; D015891:Cystatins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C498048:Rhox5 protein, mouse; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; C550521:cystatin F, mouse; C105606:phospholipase D2; D010739:Phospholipase D
Metastasis; differential gene expression; lymphoma; phospholipase D