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

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 hypothesiz... Full description

Journal Title: Journal of immunology (Baltimore Md. : 1950), October 15, 2005, Vol.175(8), pp.5351-5357
Main Author: Mestas, Javier
Other Authors: Burdick, Marie D , Reckamp, Karen , Pantuck, Allan , Figlin, Robert A , Strieter, Robert M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0022-1767
Link: http://search.proquest.com/docview/68664879/?pq-origsite=primo
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title: The role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma.
format: Article
creator:
  • Mestas, Javier
  • Burdick, Marie D
  • Reckamp, Karen
  • Pantuck, Allan
  • Figlin, Robert A
  • Strieter, Robert M
subjects:
  • Animals–Blood Supply
  • Carcinoma, Renal Cell–Genetics
  • Disease Models, Animal–Metabolism
  • Flow Cytometry–Pathology
  • Humans–Genetics
  • Kinetics–Immunology
  • Ligands–Pathology
  • Mice–Genetics
  • Mice, Inbred Balb C–Immunology
  • Mice, Knockout–Metabolism
  • Neoplasm Metastasis–Deficiency
  • Neovascularization, Pathologic–Metabolism
  • Receptors, Interleukin-8b–Physiology
  • Tumor Cells, Cultured–Physiology
  • Abridged
  • Ligands
  • Receptors, Interleukin-8b
ispartof: Journal of immunology (Baltimore, Md. : 1950), October 15, 2005, Vol.175(8), pp.5351-5357
description: 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 super(+) 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 super(+/+) mice. However, there was a marked reduction of RENCA tumor growth in CXCR2 super(-/-) 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 super(-/-) mice. These data support the notion that CXCR2/CXCR2 ligand biology is an important component of RCC tumor-associated angiogenesis and tumorigenesis.
language: eng
source:
identifier: ISSN: 0022-1767
fulltext: fulltext
issn:
  • 00221767
  • 0022-1767
url: Link


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titleThe role of CXCR2/CXCR2 ligand biological axis in renal cell carcinoma.
creatorMestas, Javier ; Burdick, Marie D ; Reckamp, Karen ; Pantuck, Allan ; Figlin, Robert A ; Strieter, Robert M
contributorMestas, Javier (correspondence author) ; Mestas, Javier (record owner)
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identifierISSN: 0022-1767
subjectAnimals–Blood Supply ; Carcinoma, Renal Cell–Genetics ; Disease Models, Animal–Metabolism ; Flow Cytometry–Pathology ; Humans–Genetics ; Kinetics–Immunology ; Ligands–Pathology ; Mice–Genetics ; Mice, Inbred Balb C–Immunology ; Mice, Knockout–Metabolism ; Neoplasm Metastasis–Deficiency ; Neovascularization, Pathologic–Metabolism ; Receptors, Interleukin-8b–Physiology ; Tumor Cells, Cultured–Physiology ; Abridged ; Ligands ; Receptors, Interleukin-8b
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descriptionRenal 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 super(+) 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 super(+/+) mice. However, there was a marked reduction of RENCA tumor growth in CXCR2 super(-/-) 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 super(-/-) mice. These data support the notion that CXCR2/CXCR2 ligand biology is an important component of RCC tumor-associated angiogenesis and tumorigenesis.
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