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(American Journal of Pathology. 2001;159:1405-1414.)
© 2001 American Society for Investigative Pathology

Regular Articles

Tumor Angiogenesis Induced by Granulocyte Chemotactic Protein-2 as a Countercurrent Principle

Els Van Coillie*, Ilse Van Aelst*, Anja Wuyts*, Roeland Vercauteren*, Rita Devos{dagger}, Chris De Wolf-Peeters{dagger}, Jo Van Damme* and Ghislain Opdenakker*

From the Laboratory of Molecular Immunology,*
Rega Institute for Medical Research, and the Laboratory of Morphology and Molecular Pathology,{dagger}
University of Leuven, Leuven, Belgium

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.




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