title: Galectin-1 upregulates CXCR4 to promote tumor progression and poor outcome in kidney cancer.
abstract: 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.
authors: Department of Biotechnology and Laboratory Science in Medicine, Infection and Immunity Center, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;
authors: Chang-Shuo
authors: CS
authors: Huang
authors: Institute of Marine Biotechnology, National Taiwan Ocean University, Keelung, Taiwan;
authors: Shye-Jye
authors: SJ
authors: Tang
authors: Department of Biotechnology and Laboratory Science in Medicine, Infection and Immunity Center, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;
authors: Ling-Yen
authors: LY
authors: Chung
authors: Biobank Management Center, Graduate Institute of Pathology and Parasitology, and.
authors: Cheng-Ping
authors: CP
authors: Yu
authors: Biobank Management Center, Graduate Institute of Pathology and Parasitology, and.
authors: Jar-Yi
authors: JY
authors: Ho
authors: Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; and.
authors: Tai-Lung
authors: TL
authors: Cha
authors: Division of Urology, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan.
authors: Chii-Cheng
authors: CC
authors: Hsieh
authors: Division of Urology, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan.
authors: Hsiao-Hsien
authors: HH
authors: Wang
authors: Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; and khsun@ym.edu.tw ghsun@mail.ndmctsgh.edu.tw.
authors: Guang-Huan
authors: GH
authors: Sun
authors: Department of Biotechnology and Laboratory Science in Medicine, Infection and Immunity Center, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; khsun@ym.edu.tw ghsun@mail.ndmctsgh.edu.tw.
authors: Kuang-Hui
authors: KH
authors: Sun
mesh_terms: D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology*; D018450:Disease Progression; D037483:Galectin 1 / Q000502:physiology*; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000502:physiology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C527276:CXCR4 protein, human; D037483:Galectin 1; D019718:Receptors, CXCR4
keywords: chemokine receptor; renal carcinoma; survival