Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis

• Published in: British journal of cancer 2014-02, Vol.110 (3), p.741-752
• Main Authors: Chen, C, Duckworth, C A, Fu, B, Pritchard, D M, Rhodes, J M, Yu, L-G
• Format: Article
• Language: English
• Subjects: 631/250/127/98; 692/699/67/2328; 692/699/67/322; 692/699/67/580; Angiogenesis; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cell adhesion & migration; Chemokine CCL2 - secretion; Chemokine CXCL1 - secretion; Chemokines; Colon; Cytokines; Drug Resistance; Endothelium; Epidemiology; Galectin 2 - blood; Galectin 4 - blood; Galectins - blood; Granulocyte Colony-Stimulating Factor - secretion; Granulocytes; Humans; Interleukin-6 - genetics; Medical research; Medical sciences; Melanoma; Metastasis; Mice; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis - pathology; Neoplasms - blood; Neoplasms - genetics; Neoplastic Cells, Circulating; Neovascularization, Pathologic - blood; Neovascularization, Pathologic - genetics; Oncology; Proteins; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.793

Background: Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GRO α )/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis. Methods: The effect of galectins-2, -4 and -8, whose circulating levels are highly increased in cancer patients, on endothelial secretion of cytokines was assessed in vitro by cytokine array and in mice. The relationship between serum levels of galectins and cytokines was analysed in colon and breast cancer patients. Results: Galectins-2, -4 and -8 at pathological concentrations induce secretion of G-CSF, IL-6, MCP-1 and GRO α from the blood vascular endothelial cells in vitro and in mice. Multiple regression analysis indicates that increased circulation of these galectins accounts for 41∼83% of the variance of these cytokines in the sera of colon and breast cancer patients. The galectin-induced secretion of these cytokines/chemokines is shown to enhance the expression of endothelial cell surface adhesion molecules, causing increased cancer-endothelial adhesion and increased endothelial tubule formation. Conclusion: The increased circulation of galectins -2, -4 and -8 in cancer patients contributes substantially to the increased circulation of G-CSF, IL-6 and MCP-1 by interaction with the blood vascular endothelium. These cytokines and chemokines in turn enhance endothelial cell activities in angiogenesis and metastasis.