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Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
- Source :
- Molecular Cancer, Molecular Cancer, Vol 5, Iss 1, p 56 (2006)
- Publication Year :
- 2006
- Publisher :
- BioMed Central, 2006.
-
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.
- Subjects :
- Transcriptional Activation
Cancer Research
Receptors, CXCR4
Stromal cell
Angiogenesis
Mice, SCID
Biology
urologic and male genital diseases
CXCR4
lcsh:RC254-282
Metastasis
03 medical and health sciences
Cytokeratin
Mice
0302 clinical medicine
Renal cell carcinoma
Cell Line, Tumor
Carcinoma
medicine
Biomarkers, Tumor
Animals
Humans
Promoter Regions, Genetic
neoplasms
Carcinoma, Renal Cell
030304 developmental biology
0303 health sciences
Gene knockdown
Research
Chemotaxis
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Hypoxia-Inducible Factor 1, alpha Subunit
female genital diseases and pregnancy complications
Cell Hypoxia
Chemokine CXCL12
Kidney Neoplasms
3. Good health
Gene Expression Regulation, Neoplastic
Oncology
Von Hippel-Lindau Tumor Suppressor Protein
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Keratins
RNA Interference
Chemokines, CXC
Subjects
Details
- Language :
- English
- ISSN :
- 14764598
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer
- Accession number :
- edsair.doi.dedup.....7f85614ab9b853c00153a393487b9d98