Diabetes mellitus potentiates diffuse large B‑cell lymphoma via high levels of CCL5

Zhang,Jingcheng; Luo,Jia; Liu,Fanrong; Wu,Dongmei; Zhong,Qingling; Zeng,Liangtao; Wu,Ziqing; Zhao,Tong; Wu,Liqing; Hao,Hua

doi:10.3892/mmr.2014.2341

Diabetes mellitus potentiates diffuse large B‑cell lymphoma via high levels of CCL5

Authors:
- Jingcheng Zhang
- Jia Luo
- Fanrong Liu
- Dongmei Wu
- Qingling Zhong
- Liangtao Zeng
- Ziqing Wu
- Tong Zhao
- Liqing Wu
- Hua Hao
View Affiliations

Affiliations: Department of Pathology, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China , College of Nursing, Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: June 17, 2014 https://doi.org/10.3892/mmr.2014.2341
Pages: 1231-1236

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

There is much evidence suggesting that CCL5 is one of the chemoattractant cytokines involved in diabetes mellitus (DM) with diffuse large B‑cell lymphoma (DLBCL). However, the pathological impact is unclear. In the current study, in order to improve understanding regarding the role of CCL5 in DM with DLBCL, the expression levels of CCL5 mRNA were examined in normal B cells, human DLBCL cell lines (Ly1, Ly8 and Ly10) and a mouse DLBCL cell line (A20), as well as those in cells cultured with either 5 or 30 mmol/l glucose. A20‑CCL5+ (CCL5 overexpression) and A20‑CCL5‑ (CCL5 knockdown) subclones were obtained through cell transduction with a lentiviral vector, and were subcutaneously injected into BALB/c DM mice and normal mice. Tumor growth was observed by calculating the tumor volume. The results demonstrated that CCL5 mRNA levels in DLBCL cells were significantly higher than those in the normal cells (P<0.05); and levels in DLBCL cells in 30 mmol/l Glu were significantly higher than in those of DLBCL cells in 5 mmol/l Glu (P<0.05). A20‑CCL5+ cells led to tumor formation in DM mice compared with A20 and A20‑CCL5‑ cells. These results indicate that high levels of CCL5 expression may accelerate DLBCL formation in DM.

View Figures

View References

1	Renehan AG, Tyson M, Egger M, et al: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 371:569–578. 2008. View Article : Google Scholar : PubMed/NCBI
2	Mitri J, Castillo J and Pittas AG: Diabetes and risk of Non-Hodgkin’s lymphoma: a meta-analysis of observational studies. Diabetes Care. 31:2391–2397. 2008.
3	Nakajima K, Tanaka Y, Nomiyama T, et al: RANTES promoter genotype is associated with diabetic nephropathy in type 2 diabetic subjects. Diabetes Care. 26:892–898. 2003. View Article : Google Scholar : PubMed/NCBI
4	Herder C, Peltonen M, Koenig W, et al: Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study. Diabetes. 55:2340–2346. 2006. View Article : Google Scholar : PubMed/NCBI
5	Lehmann MH, Schreiber S, Vogelsang H and Sigusch HH: Constitutive expression of MCP-1 and RANTES in the human histiocytic lymphoma cell line U-937. Immunol Lett. 76:111–113. 2001. View Article : Google Scholar : PubMed/NCBI
6	Liu F, Zhang Y, Wu ZQ and Zhao T: Analysis of CCL5 expression in classical Hodgkin’s lymphoma L428 cell line. Mol Med Rep. 4:837–841. 2011.
7	Liu FR, Zhong QL, Liu DW, et al: Establishment of type 1 diabetic BALB/c mouse models and detection of CD4⁺CD25⁺regulatory T cells. Guangdong Med J. 32:427–429. 2011.(In Chinese).
8	Zhong QL, Liu FR, Liu DW, et al: Expression of β-catenin and cyclin D1 in epidermal stem cells of diabetic rats. Mol Med Rep. 4:377–381. 2011.
9	Kraan MC, Smith MD, Weedon H, et al: Measurement of cytokine and adhesion molecule expression in synovial tissue by digital image analysis. Ann Rheum Dis. 60:296–298. 2001. View Article : Google Scholar : PubMed/NCBI
10	Carvalho-Pinto C, García MI, Gómez L, et al: Leukocyte attraction through the CCR5 receptor controls progress from insulitis to diabetes in non-obese diabetic mice. Eur J Immunol. 34:548–557. 2004. View Article : Google Scholar : PubMed/NCBI
11	Bogdanski P, Pupek-Musialik D, Dytfeld J, et al: Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus. Int J Clin Pharmacol Ther. 45:563–567. 2007. View Article : Google Scholar : PubMed/NCBI
12	Ando H, Kurita S and Takamura T: The specific p38 mitogen-activated protein kinase pathway inhibitor FR167653 keeps insulitis benign in nonobese diabetic mice. Life Sci. 74:1817–1827. 2004. View Article : Google Scholar : PubMed/NCBI
13	Nakamura K, Yamagishi S, Adachi H, et al: Serum levels of sRAGE, the soluble form of receptor for advanced glycation end products, are associated with inf1ammatory markers in patients with type 2 diabetes. Mol Med. 13:185–189. 2007. View Article : Google Scholar
14	Kulbe H, Levinson NR, Balkwill F and Wilson JL: The chemokine network in cancer - much more than directing cell movement. Int J Dev Biol. 48:489–496. 2004. View Article : Google Scholar : PubMed/NCBI
15	Soria G and Ben-Baruch A: The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 267:271–285. 2008. View Article : Google Scholar : PubMed/NCBI
16	Adler EP, Lemken CA, Katchen NS and Kurt RA: A dual role for tumor-derived chemokine RANTES (CCL5). Immunol Lett. 90:187–194. 2003. View Article : Google Scholar : PubMed/NCBI
17	Brownlee M: The pathobiology of diabetes complications: a unifying mechanism. Diabetes. 54:1615–1625. 2005. View Article : Google Scholar : PubMed/NCBI
18	Goodwin PJ, Ennis M, Pritchard KI, et al: Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 20:42–51. 2002. View Article : Google Scholar : PubMed/NCBI
19	Saydah SH, Loria CM, Eberhardt MS and Brancati FL: Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol. 157:1092–1100. 2003. View Article : Google Scholar : PubMed/NCBI
20	Richardson LC and Pollack LA: Therapy insight: Influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol. 2:48–53. 2005. View Article : Google Scholar : PubMed/NCBI
21	Mueller CG, Boix C, Kwan WH, et al: Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation. J Leukoc Biol. 82:567–575. 2007. View Article : Google Scholar : PubMed/NCBI
22	Skinnider BF and Mak TW: The role of cytokines in classical Hodgkin lymphoma. Blood. 99:4283–4297. 2002. View Article : Google Scholar : PubMed/NCBI
23	Aldinucci D, Lorenzon D, Cattaruzza L, et al: Expression of CCR5 receptors on Reed-Steinberg cells and Hodgkin lymphoma cell lines: involvement of CCL5/Rantes in tumor cell growth and microenvironmental interactions. Int J Cancer. 122:769–776. 2008. View Article : Google Scholar
24	Fischer M, Juremalm M, Olsson N, et al: Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue. Int J Cancer. 107:197–201. 2003. View Article : Google Scholar : PubMed/NCBI
25	Appay V and Rowland-Jones SL: RANTES: a versatile and controversial chemokine. Trends Immunol. 22:83–87. 2001. View Article : Google Scholar : PubMed/NCBI
26	Sun N, Yang G, Zhao H, et al: Multidose streptozotocin induction of diabetes in BALB/c mice induces a dominant oxidative macrophage and a conversion of THl to TH2 phenotypes during disease progression. Mediators Inflamm. 2005:202–209. 2005. View Article : Google Scholar
27	Bernardi R, Grisendi S and Pandolfi PP: Modelling haematopoietic malignancies in the mouse and therapeutical implications. Oncogene. 21:3445–3458. 2002. View Article : Google Scholar