American Association for Cancer Research
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10780432ccr122940-sup-ccr-12-2940tab1fig1.pdf (106.42 kB)

Supplementary Table 1 and Figure 1 from Increased Circulation of Galectin-3 in Cancer Induces Secretion of Metastasis-Promoting Cytokines from Blood Vascular Endothelium

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posted on 2023-03-31, 18:18 authored by Chen Chen, Carrie A. Duckworth, Qicheng Zhao, David Mark Pritchard, Jonathan M. Rhodes, Lu-Gang Yu

PDF file - 106K, Table S1: Characteristics of the colorectal cancer patients; Fig S1: Effect of low and high galectin-3-containing human serum on cytokine secretion from HMVECs.

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ARTICLE ABSTRACT

Purpose: Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer.Experimental Design: The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3–induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated.Results: Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinαvβ1, E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell–endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations.Conclusion: The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival. Clin Cancer Res; 19(7); 1693–704. ©2013 AACR.