The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein–Barr virus-transformed lymphoblastoid cells

Kimura, Ryosuke; Nishioka, Tomoki; Ishida, Takeshi

doi:10.1038/sj.gene.6363978

Cited by 22 publications

(18 citation statements)

References 26 publications

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“…In agreement with our prior data CXCR4 protein expression was similarly observed in isolated crypts from human colonic tissues (data not shown). Isolated human peripheral blood monocytes assayed as a control did not express CXCL12 (Kimura et al, 2003). Those data, combined with the amplification of villin and CD45 as control transcripts, indicate that CXCL12 and CXCR4 mRNA expression observed in our mucosal preparations solely reflected epithelial expression and was not the result of contaminating immune cells.…”

Section: Resultsmentioning

confidence: 64%

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

et al. 2006

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Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinomaderived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2 0 -deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.

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Section: Resultsmentioning

confidence: 64%

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

et al. 2006

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“…Similarly, Kimura et al 21 did not detect a significant association between the CXCL12 gene polymorphism and gene expression (CXCL12 mRNA levels) in EBV-transformed lymphoblastic cell lines. Their more recent study 22 on EBV-transformed lymphoblastic cell lines with a heterozygous CXCL12 genotype demonstrated that the polymorphisms other than the CXCL12 G801A polymorphism could have a cis-acting effect on the expression of CXCL12 transcripts.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, our results regarding patients undergoing autologous transplantation of haematopoietic stem cells concur with those reported by Benboubker et al 15 The association between the CXCL12 gene polymorphism and the serum levels of CXCL12vwas suggested by Winkler et al 11 However, to date, the exact relationship between the CXCL12 genotypes and the corresponding protein production is not clear and the studies examining the association differ in their methodological approaches. [20][21][22][23] As this mutation lies in the 3 0 UTR of the gene, Winkler et al 11 suggested that this mutation may upregulate transcription of the gene, resulting in more abundant CXCL12, which in turn, inhibits T-tropic HIV-1 and delays the onset of the disease. Arya et al 20 tested this hypothesis in vitro: the wild-type and the mutant CXCL12 gene were cloned and the expression was measured in human and insect cells in culture.…”

Section: Discussionmentioning

confidence: 99%

The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

Bogunia‐Kubik

Gieryng

Dłubek

et al. 2009

Bone Marrow Transplant

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The interaction between CXCL12 and its receptor CXCR4 plays a crucial role in the homing and mobilization of haematopoietic progenitors. We investigated the putative association between a CXCL12 gene polymorphism, the G-A transition at position 801 in the 3 0 -untranslated region (3 0 UTR), and the yield of CD34 þ progenitors in 65 healthy allogeneic transplant donors who received G-CSF. Importantly, in this setting, the analysis was not biased by background disease or chemotherapy. The 3 0 UTR CXCL12 G801A polymorphism was detected using a PCR-RFLP technique with the MspI restriction enzyme and the frequency of CD34 þ progenitors was assessed by flow cytometry. The frequency as well as the number of CD34 þ progenitor cells in the first leukapheresis product was significantly higher from donors with the CXCL12-3 0 A allele compared to GG homozygotes (Po0.05 in both cases), especially for subjects with the CXCL12-3 0 AA homozygous genotype (Po0.01 in both cases). Moreover, more leukaphereses were needed to obtain the required number of CD34 þ progenitors for transplantation from CXCL12-3 0 GG homozygous donors compared to the CXCL12-3 0 A carriers (P ¼ 0.003). In conclusion, the CXCL12-3 0 A allele was associated with a higher yield of CD34 þ cells from healthy donors of PBPC for allogeneic haematopoietic SCT.

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“…The lack of both CXCR4 and CXCL12 expression by the MDA-MB-435s cell line may reflect their clarification not as mammary carcinoma cells but as melanoma cells (Ellison et al, 2002). Thus, the expression profile acquired during mammary epithelial transformation was characteristically similar to highly migratory leukocytes in that CXCR4 expression predominates over little if any CXCL12 expression (Kimura et al, 2003).…”

Section: Loss Of Cxcl12 Expression In Mammary Carcinomamentioning

confidence: 98%

Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells

2007

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Expression of the chemokine receptor CXCR4 has been linked with increased metastasis and decreased clinical prognosis in breast cancer. The current paradigm dictates that CXCR4 fosters carcinoma cell metastasis along a chemotactic gradient to organs expressing the ligand CXCL12. The present study asked if alterations in autocrine CXCR4 signaling via dysregulation of CXCL12 in mammary carcinoma cells modulated their metastatic potential. While CXCR4 was consistently detected, expression of CXCL12 characteristic of human mammary epithelium was silenced by promoter hypermethylation in breast cancer cell lines and primary mammary tumors. Stable re-expression of functional CXCL12 in ligand null cells increased orthotopic primary tumor growth in the mammary fat-pad model of tumorigenesis. Those data parallel increased carcinoma cell proliferation measured in vitro with little-to-no-impact on apoptosis. Moreover, re-expression of autocrine CXCL12 markedly reduced metastatic lung invasion assessed using in vivo bioluminescence imaging following tail vein injection. Consistent with those data, decreased metastasis reflected diminished intracellular calcium signaling and chemotactic migration in response to exogenous CXCL12 independent of changes in CXCR4 expression. Together these data suggest that an elevated migratory signaling response to ectopic CXCL12 contributes to the metastatic potential of CXCR4-expressing mammary carcinoma cells, subsequent to epigenetic silencing of autocrine CXCL12.

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The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein–Barr virus-transformed lymphoblastoid cells

Cited by 22 publications

References 26 publications

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis

The CXCL12-3′A allele is associated with a higher mobilization yield of CD34 progenitors to the peripheral blood of healthy donors for allogeneic transplantation

Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells

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