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Molecular Cancer
Published in: Molecular Cancer 1/2006

Open Access 01-12-2006 | Research

Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis

Authors: Judong Pan, Javier Mestas, Marie D Burdick, Roderick J Phillips, George V Thomas, Karen Reckamp, John A Belperio, Robert M Strieter

Published in: Molecular Cancer | Issue 1/2006

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Abstract

Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor protein, or incubating the cells under hypoxic conditions. The enhanced CXCR4 expression was mediated through the interaction of the Hypoxia Inducible Factor-1α (HIF-1α) with the promoter region of the CXCR4 gene. Furthermore, the expression of CXCR4 on human RCC directly correlated with their metastatic ability in vivo in both heterotopic and orthotopic SCID mouse models of human RCC. Neutralization of CXCL12 in SCID mice abrogated metastasis of RCC to target organs expressing high levels of CXCL12; without altering tumor cell proliferation, apoptosis, or tumor-associated angiogenesis. Therefore, our data suggest that the CXCL12/CXCR4 biological axis plays an important role in regulating the organ-specific metastasis of RCC.
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Metadata
Title
Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
Authors
Judong Pan
Javier Mestas
Marie D Burdick
Roderick J Phillips
George V Thomas
Karen Reckamp
John A Belperio
Robert M Strieter
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2006
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-5-56

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