Isotypic neutralizing antibodies against mouse GCP-2/CXCL6 inhibit melanoma growth and metastasis

• Published in: Cancer letters 2011-03, Vol.302 (1), p.54-62
• Main Authors: Verbeke, Hannelien, Struyf, Sofie, Berghmans, Nele, Van Coillie, Els, Opdenakker, Ghislain, Uyttenhove, Catherine, Van Snick, Jacques, Van Damme, Jo
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - pharmacology; blood circulation; Bone cancer; Cancer therapies; Cell culture; Cell Line, Tumor; Cell Proliferation - drug effects; chemoattractants; Chemokine; Chemokine CXCL6 - genetics; Chemokine CXCL6 - immunology; Chemokine CXCL6 - metabolism; Chemokines; chemotaxis; Chemotaxis, Leukocyte - drug effects; Cytotoxicity; Female; Granulocyte chemotactic protein-2 (GCP-2); Granulocytes - drug effects; Granulocytes - metabolism; half life; Hematology, Oncology and Palliative Medicine; Humans; Melanoma; Melanoma - genetics; Melanoma - pathology; Melanoma - prevention & control; Melanoma, Experimental - genetics; Melanoma, Experimental - metabolism; Melanoma, Experimental - prevention & control; Metastasis; Mice; Mice, Inbred Strains; Mice, Nude; Neoplasm Metastasis; neutralization; neutralizing antibodies; Proteins; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2010.12.013

Abstract The chemokine granulocyte chemotactic protein (GCP)-2/CXCL6 promotes tumor growth as angiogenesis inducer and neutrophil chemoattractant. The neutralizing capacity and specificity of monoclonal mouse anti-murine (mu)GCP-2/CXCL6 antibodies were evidenced by granulocyte chemotaxis and signaling assays. The half-life of the non-antigenic antibody in the blood circulation was approximately 15 days. The titers remained constant upon weekly injection. Tumor growth and lymphogenic metastases of human melanoma over-expressing muGCP-2 were reduced in mice treated with anti-muGCP-2. Moreover, the drop in muGCP-2 antibody titer correlated with the melanoma tumor size. Taken together, we show that functional blocking of GCP-2 inhibits tumor growth and metastases.