Tumor angiogenesis induced by granulocyte chemotactic protein-2 as a countercurrent principle.
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.
Van Coillie
E
E
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Van Aelst
I
I
Wuyts
A
A
Vercauteren
R
R
Devos
R
R
De Wolf-Peeters
C
C
Van Damme
J
J
Opdenakker
G
G
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
C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D010446:Peptide Fragments; D011994:Recombinant Proteins