Upregulation of the Chemokine Receptor CCR2B in Epstein‒Barr Virus-Positive Burkitt Lymphoma Cell Lines with the Latency III Program

Abstract

CCR2 is the cognate receptor to the chemokine CCL2. CCR2–CCL2 signaling mediates cancer progression and metastasis dissemination. However, the role of CCR2–CCL2 signaling in pathogenesis of B-cell malignancies is not clear. Previously, we showed that CCR2B was upregulated in ex vivo peripheral blood B cells upon Epstein‒Barr virus (EBV) infection and in established lymphoblastoid cell lines with the EBV latency III program. EBV latency III is associated with B-cell lymphomas in immunosuppressed patients. The majority of EBV-positive Burkitt lymphoma (BL) tumors are characterized by latency I, but the BL cell lines drift towards latency III during in vitro culture. In this study, the CCR2A and CCR2B expression was assessed in the isogenic EBV-positive BL cell lines with latency I and III using RT-PCR, immunoblotting, and immunostaining analyses. We found that CCR2B is upregulated in the EBV-positive BL cells with latency III. Consequently, we detected the migration of latency III cells toward CCL2. Notably, the G190A mutation, corresponding to SNP CCR2-V64I, was found in one latency III cell line with a reduced migratory response to CCL2. The upregulation of CCR2B may contribute to the enhanced migration of malignant B cells into CCL2-rich compartments.

Expression of the Chemokine Receptor CCR1 in Burkitt Lymphoma Cell Lines Is Linked to the CD10-Negative Cell Phenotype and Co-Expression of the EBV Latent Genes EBNA2, LMP1, and LMP2

“…By comparison, in LCL-2mon cells, the value was 0.111 ± 0.031 ( Figure 1 A). We also demonstrated previously that CCR2 (isoform CCR2B ) was expressed and that the receptor was functional in LCLs and in three endemic BL cell lines (Mutu cl.99, Mutu III, and Jijoye P79), in which the EBV-encoded latent protein EBNA2 is abundantly expressed [ 23 ] ( Figure 2 D).…”

Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis

“…EBV-associated B cell lymphomas express three latent types (I, II, or III), which type of latency depends on the B cell stage of tumor origin. The majority of EBV-positive Burkitt lymphomas (BL) is characterized by latency I, but some BL cell lines drift towards latency III during culture in vitro, such as Raji cells [15, 16]. In contrast, EBV infection does not induce clonal expansion in primary epithelial cells, all EBV-associated epithelial cancers express a latency II programme [17].…”

Evolution of CCR5 and CCR2 Genes in Bats Showed Multiple Independent Gene Conversion Events

“…This hypothesis relies heavily on the existence of pathogens that are able to hijack chemokine receptors and use them to enter the cell. Some examples of such pathogens have indeed been identified, such as HIV-1, dengue virus (DENV), Epstein-Barr virus (EBV), and Plasmodium vivax [4][5][6][7][8][9][10][11]. Although DENV and EBV interactions with chemokine receptors remain somewhat elusive, it is well established that both HIV-1 and Plasmodium vivax interact directly with chemokine receptors in order to infect the cell [4,5,7,10,11].…”

“…Chemokine receptors are expressed in lymphocytes, neutrophils, dendritic cells, and many other cell types, and play a part in both the innate and adaptive immune responses, being mainly involved in the trafficking of leukocyte populations to a site of injury and/or infection [1]. Additionally, some of these receptors have been deemed as determinants of infectiousness for different pathogens [4][5][6][7][8][9][10][11]. Most notably, CCR5 and CXCR4 have both been identified as vital co-receptors that mediate human immunodeficiency virus (HIV) entry into human cells [10][11][12][13].…”