Structure and Chromosomal Localization of the Human Stromal Cell-Derived Factor 1 (SDF1) Gene

Shirozu, Michio; Nakano, Toru; Inazawa, Johji; Tashiro, Kei; Tada, Hideaki; Shinohara, Takashi; Honjo, Tasuku

doi:10.1006/geno.1995.1180

Cited by 554 publications

(446 citation statements)

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“…The ubiquitous expression of CXCL12 is consistent with the presence of TATA-less and GC-rich sequences in the 5'-flanking region, as is often found in so-called 'housekeeping genes' (Shirozu et al, 1995). Recent studies indicate that CXCL12 expression is markedly decreased in rapidly dividing fibroblasts and liver cells (Jiang et al, 1994), premalignant colonic adenomas, hepatocellular carcinomas (Shibuta et al, 1997), as well as in various malignant cell lines (Begum et al, 1996(Begum et al, , 1999.…”

supporting

confidence: 63%

CXCR4/CXCL12 expression and signalling in kidney cancer

et al. 2002

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CXCL12 (SDF-1), a CXC-chemokine, and its specific receptor, CXCR4, have recently been shown to be involved in tumourgenesis, proliferation and angiogenesis. Therefore, we analysed CXCL12α/CXCR4 expression and function in four human kidney cancer cell lines (A-498, CAKI-1, CAKI-2, HA-7), 10 freshly harvested human tumour samples and corresponding normal kidney tissue. While none of the analysed tumour cell lines expressed CXCL12α, A-498 cells were found to express CXCR4. More importantly, real-time RT–PCR analysis of 10 tumour samples and respective adjacent normal kidney tissue disclosed a distinct and divergent downregulation of CXCL12α and upregulation of CXCR4 in primary tumour tissue. To prove that the CXCR4 protein is functionally active, rhCXCL12α was investigated for its ability to induce changes of intracellular calcium levels in A-498 cells. Moreover, we used cDNA expression arrays to evaluate the biological influence of CXCL12α. Comparing gene expression profiles in rhCXCL12α stimulated vs unstimulated A-498 kidney cancer cells revealed specific regulation of 31 out of 1176 genes tested on a selected human cancer array, with a prominent stimulation of genes involved in cell-cycle regulation and apoptosis. The genetic changes reported here should provide new insights into the developmental paths leading to tumour progression and may also aid the design of new approaches to therapeutic intervention. British Journal of Cancer (2002) 86 , 1250–1256. DOI: 10.1038/sj/bjc/6600221 www.bjcancer.com © 2002 Cancer Research UK

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supporting

confidence: 63%

CXCR4/CXCL12 expression and signalling in kidney cancer

et al. 2002

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“…[8][9][10] The physiological receptors of CXCL12 are CXCR4 and CXCR7, 8 but only CXCR4 is involved in haematopoiesis. CXCR4 is a G-protein-coupled seven-transmembrane receptor present on the CD34 þ cells.…”

Section: Introductionmentioning

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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“…In contrast to CXCR4, the role for autocrine expression of its ligand CXCL12 in carcinogenesis remains to be established (Wendt et al, 2006). We and others have previously observed that several normal epithelial tissues express not only CXCR4 but also the ligand CXCL12 (Shirozu et al, 1995;Wendt et al, 2006). Genes such as CXCL12 with a high occurrence of CpG dinucleotides in the promoter region are subject to transcriptional silencing via cytosine methylation (Herman and Baylin, 2003).…”

Section: Introductionmentioning

confidence: 99%

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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Structure and Chromosomal Localization of the Human Stromal Cell-Derived Factor 1 (SDF1) Gene

Cited by 554 publications

References 0 publications

CXCR4/CXCL12 expression and signalling in kidney cancer

CXCR4/CXCL12 expression and signalling in kidney cancer

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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