Abstract
The aim of our study was to analyse the expression of CXCL16, ADAM10 and CXCR6 in
renal cell carcinoma (RCC) tissue and to correlate the expression pattern with clinicopathologic
data, including patient survival. Furthermore, we investigated CXCL16, ADAM10 and
CXCR6 expressions by FACS, immunofluorescence and ELISA analysis in renal carcinoma
cell lines. Our immunohistochemical analysis on tissue microarray of renal cancer
samples of 104 patients revealed that ADAM10 correlated significantly with tumour
stage, pathological nodal status, M status and lymphangiosis carcinomatosa. CXCL16,
CXCR6 and ADAM10 were significantly increased in papillary carcinomas. Importantly,
high levels of CXCL16 expression in renal cancer tissue correlated with better survival
of patients, and CXCL16 correlated inversely to the tumour stage. In addition, inhibition
of CXCL16 induced the migration of renal cancer cells assuming an anti-migratory function
of transmembrane CXCL16. Taken together, our data demonstrate that downregulation
of CXCL16 plays an important role in renal cancer development and progression, and
that CXCL16 in RCC is an independent prognostic marker for better patient survival.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Renal cell carcinoma: current status and future prospects.Cancer Treat Rev. 2005; 31: 536-545
- The changing natural history of renal cell carcinoma.J Urol. 2001; 166: 1611-1623
- Chemokines in tumor progression and metastasis.Cancer Sci. 2005; 96: 317-322
- Anti-tumor responses induced by chemokine CCL19 transfected into an ovarian carcinoma model via fiber-mutant adenovirus vector.Biol Pharm Bull. 2005; 28: 1066-1070
- SLC/CCL21-mediated anti-tumor responses require IFNgamma, MIG/CXCL9 and IP-10/CXCL10.Mol Cancer. 2003; 2: 22
- High-level expression of chemokine CXCL16 by tumor cells correlates with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer.Cancer Res. 2007; 67: 4725-4731
- Regulated shedding of transmembrane chemokines by the disintegrin and metalloproteinase 10 facilitates detachment of adherent leukocytes.J Immunol. 2007; 178: 8064-8072
- Enhanced expression and shedding of the transmembrane chemokine CXCL16 by reactive astrocytes and glioma cells.J Neurochem. 2005; 93: 1293-1303
- Constitutive expression and regulated release of the transmembrane chemokine CXCL16 in human and murine skin.J Invest Dermatol. 2007; 127: 1444-1455
- Expression of CXCL16 in human rectal cancer.Int J Mol Med. 2004; 14: 65-69
- Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells.J Leukoc Biol. 2004; 75: 267-274
- The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10.J Immunol. 2004; 172: 6362-6372
- Metalloproteinase inhibitors for the disintegrin-like metalloproteinases ADAM10 and ADAM17 that differentially block constitutive and phorbol ester-inducible shedding of cell surface molecules.Comb Chem High Throughput Screen. 2005; 8: 161-171
- Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma.Brit J Cancer. 2008; 98: 496-501
- Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer.Eur J Cancer. 2001; 37: 1089-1095
- Molecular characterization of a novel, widespread nuclear protein that colocalizes with spliceosome components.Mol Biol Cell. 1998; 9: 143-160
- Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene.Am J Pathol. 2001; 159: 1635-1643
- Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney.Kidney Int. 2008;
- Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.Nature. 2001; 411: 494-498
- Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.J Cell Biol. 2001; 155: 661-673
- Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by alpha- and gamma-secretases.Biochem Biophys Res Commun. 2007; 358: 233-240
- STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1.J Exp Med. 1997; 185: 2015-2023
- Spontaneous regression of metastatic renal cell carcinoma.Urology. 1982; 20: 177-181
- Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma.J Clin Oncol. 2005; 23: 133-141
- Renal cell carcinoma: new developments in molecular biology and potential for targeted therapies.Oncologist. 2007; 12: 1404-1415
- Epigenetics in cancer.N Engl J Med. 2008; 358: 1148-1159
- A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus.J Biol Chem. 2008; 283: 12691-12700
- Implication of APP secretases in notch signaling.J Mol Neurosci. 2001; 17: 171-181
- The chemokine receptor CXCR6 and its ligand CXCL16 are expressed in carcinomas and inhibit proliferation.Cancer Res. 2008; 68: 4701-4708
- CXCL16 functions as a novel chemotactic factor for prostate cancer cells in vitro.Mol Cancer Res. 2008; 6: 546-554
- Overexpression of CXCL16 and its receptor CXCR6/Bonzo promotes growth of human schwannomas.Glia. 2008; 56: 764-774
- Nuclear expression of CXCR4 in tumor cells of non-small cell lung cancer is correlated with lymph node metastasis.Human Pathol. 2008;
- Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer.Brit J Cancer. 2008; 98: 1682-1689
- The chemokine ESkine/CCL27 displays novel modes of intracrine and paracrine function.J Immunol. 2002; 169: 1387-1394
Article info
Publication history
Published online: December 15, 2008
Accepted:
October 24,
2008
Received in revised form:
October 10,
2008
Received:
July 25,
2008
Footnotes
☆Study was supported in part from the Edith von Heyden-legacy (Ac.Nr. 8599657) and the inheritance of Martha Schmelz (Ac.Nr. 8599660).
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
