title: Tumor angiogenesis induced by granulocyte chemotactic protein-2 as a countercurrent principle.
abstract: Chemokine production by tumors is a well-known phenomenon, but its role in tumor biology remains debatable. Although intratumoral injection of granulocyte chemotactic protein-2 (GCP-2) had no effect on tumor parameters, needle-free stable expression of the chemokine resulted in enhanced tumor growth. It is shown here that tumors that express a potent form of GCP-2 induce a strong influx and activation of tumor-associated neutrophils. The production of GCP-2 leads to intratumoral expression of gelatinase B and advantage for tumor growth by increased angiogenesis. These results are in line with the countercurrent principle of chemokine action and support the notion that paraneoplastic expression of ELR-positive CXC chemokines has to be blocked rather than stimulated in cancer therapy.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Coillie
authors.forename: I
authors.initials: I
authors.lastname: Van Aelst
authors.forename: A
authors.initials: A
authors.lastname: Wuyts
authors.forename: R
authors.initials: R
authors.lastname: Vercauteren
authors.forename: R
authors.initials: R
authors.lastname: Devos
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: J
authors.initials: J
authors.lastname: Van Damme
authors.forename: G
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000818:Animals; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D015552:Injections, Intralesional; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology*; D009504:Neutrophils / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D014162:Transfection
chemical_list: C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D010446:Peptide Fragments; D011994:Recombinant Proteins