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 granul ocyte chemotactic protein-2 (GCP-2) had no effect on tumor parameters, need le-free stable expression of the chemokine resulted in enhanced tumor growt h. 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 product ion 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 th at paraneoplastic expression of ELR-positive CXC chemokines has to be block ed rather than stimulated in cancer therapy.