Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

• Published in: Journal of the American Society of Nephrology 2014-07, Vol.25 (7), p.1486-1495
• Main Authors: HUANG, Chang-Shuo, TANG, Shye-Jye, CHUNG, Ling-Yen, YU, Cheng-Ping, HO, Jar-Yi, CHA, Tai-Lung, HSIEH, Chii-Cheng, WANG, Hsiao-Hsien, SUN, Guang-Huan, SUN, Kuang-Hui
• Format: Article
• Language: English
• Subjects: Basic Research; Biological and medical sciences; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Disease Progression; Galectin 1 - physiology; Humans; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Kidneys; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Prognosis; Receptors, CXCR4 - physiology; Survival Rate; Tumor Cells, Cultured; Tumors; Tumors of the urinary system; Up-Regulation
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2013070773

Galectin-1, a β-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-κB (NF-κB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-κB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease.