Issn Print: 0885-3177
Publication Date: 2008/11/01
CXCL5[ENA-78] MEDIATES PANCREATIC CANCER DERIVED ANGIOGENESIS
A. Li; R. M. Strieter; M. Sugi; H. A. Reber; G. Eibl; O. J. Hines
Excerpt
We have previously reported that the CXC chemokine CXCL5[epithelial neutrophil activating peptide-78] is markedly overexpressed in the serum and tumors of patients with pancreatic cancer. The CXC chemokine family is unique with respect to the process of angiogenesis, and angiogenesis is a key step in the progression to and maintenance of a malignant phenotype. In this study, we hypothesize that CXCL5[ENA-78] is an important regulator of pancreatic cancer angiogenic activity. Human umbilical vascular endothelial cells (HUVEC) were treated with exogenous recombinant human (rh) CXCL5[ENA-78]. We observed a dose dependent increase in HUVEC growth in response to rhCXCL5[ENA-78] treatment (p < 0.02). This response was specific to the ligand given that rhCXCL5[ENA-78] in combination with antibody to CXCL5[ENA-78] or its receptor, CXCR2, blocked HUVEC growth (IgG served as control) (p < 0.02). Conditioned media from pancreatic cancer cells (ASPC-1, BxPC-3 and MIA PaCa-2) significantly stimulated HUVEC growth (P < 0.01). The induction of HUVEC growth by pancreatic cancer cell media was blocked by antibody treatment to CXCL5[ENA-78] or CXCR2 (P < 0.03). Finally, pancreatic cancer cell conditioned media and rhCXCL5[ENA-78] both stimulated capillary tube formation, and tubule formation was inhibited by antibody treatment to CXCL5[ENA-78] or CXCR2. These results suggest that CXCL5[ENA-78] is an important mediator of angiogenesis in pancreatic cancer.
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