Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis.
A central feature of all solid tumor growth is the presence of neovascularization. The CXC chemokines GRO-gamma/CXCL3, ENA-78/CXCL5, and IL-8/CXCL8 have profound angiogenic potential mediated through the CXCR2 receptor. The aim of the present study was to evaluate the expression of the angiogenic chemokines in three human pancreatic cancer cell lines and to determine the role of these proteins in pancreatic cancer angiogenesis. Secreted CXC protein levels in the supernatant of the cell lines were analyzed by ELISA. A rat corneal micropocket model was used to determine the angiogenic potential of these secreted CXC chemokines in vivo. ELISA confirmed expression of all three tested CXC chemokines in the supernatant of two cell lines. In the corneal micropocket assay, neovascularization was induced using pelleted supernatant of all three-cell lines. Using an anti-CXCR2 antibody, neovascularization was significantly inhibited in the high expressing BxPC-3 cell line samples. In addition, the expression of ENA-78/CXCL5 and IL-8/CXCL8 has been evaluated in human pancreatic cancer tissue samples by using immunohistochemistry in order to further investigate the potential role of CXC chemokines in pancreatic cancer angiogenesis and tumorigenesis.
Wente
Moritz N
MN
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Keane
Michael P
MP
Burdick
Marie D
MD
Friess
Helmut
H
Büchler
Markus W
MW
Ceyhan
Güralp O
GO
Reber
Howard A
HA
Strieter
Robert M
RM
Hines
Oscar J
OJ
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000378:metabolism; D003315:Cornea / Q000098:blood supply; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008024:Ligands; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000628:therapy; D051381:Rats; D020318:Rats, Long-Evans; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*
D019138:Antibodies, Blocking; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016209:Interleukin-8; D008024:Ligands; D023063:Receptors, Interleukin-8B