RGD Reference Report - The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma. - Rat Genome Database

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The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma.

Authors: Mestas, J  Burdick, MD  Reckamp, K  Pantuck, A  Figlin, RA  Strieter, RM 
Citation: Mestas J, etal., J Immunol. 2005 Oct 15;175(8):5351-7.
RGD ID: 7257682
Pubmed: PMID:16210641   (View Abstract at PubMed)

Renal cell carcinoma (RCC) accounts for 3% of new cancer incidence and mortality in the United States. Studies in RCC have predominantly focused on VEGF in promoting tumor-associated angiogenesis. However, other angiogenic factors may contribute to the overall angiogenic milieu of RCC. We hypothesized that the CXCR2/CXCR2 ligand biological axis represents a mechanism by which RCC cells promote angiogenesis and facilitate tumor growth and metastasis. Therefore, we first examined tumor biopsies and plasma of patients with metastatic RCC for levels of CXCR2 ligands, and RCC tumor biopsies for the expression of CXCR2. The proangiogenic CXCR2 ligands CXCL1, CXCL3, CXCL5, and CXCL8, as well as VEGF were elevated in the plasma of these patients and found to be expressed within the tumors. CXCR2 was found to be expressed on endothelial cells within the tumors. To assess the role of ELR(+) CXC chemokines in RCC, we next used a model of syngeneic RCC (i.e., RENCA) in BALB/c mice. CXCR2 ligand and VEGF expression temporally increased in direct correlation with RENCA growth in CXCR2(+/+) mice. However, there was a marked reduction of RENCA tumor growth in CXCR2(-/-) mice, which correlated with decreased angiogenesis and increased tumor necrosis. Furthermore, in the absence of CXCR2, orthotopic RENCA tumors demonstrated a reduced potential to metastasize to the lungs of CXCR2(-/-) mice. These data support the notion that CXCR2/CXCR2 ligand biology is an important component of RCC tumor-associated angiogenesis and tumorigenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  ISOCxcr2 (Mus musculus)7257682; 7257682 RGD 
renal cell carcinoma  IMP 7257682 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Mus musculus)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Homo sapiens)
CXCR2  (C-X-C motif chemokine receptor 2)


Additional Information