Expression profiling of Galectin-3-depleted melanoma cells reveals its major role in melanoma cell plasticity and vasculogenic mimicry

Am J Pathol. 2008 Dec;173(6):1839-52. doi: 10.2353/ajpath.2008.080380. Epub 2008 Nov 6.


Galectin-3 (Gal-3) is a beta-galactoside-binding protein that is involved in cancer progression and metastasis. Using a progressive human melanoma tissue microarray, we previously demonstrated that melanocytes accumulate Gal-3 during the progression from benign to dysplastic nevi to melanoma and further to metastatic melanoma. Herein, we show that silencing of Gal-3 expression with small hairpin RNA results in a loss of tumorigenic and metastatic potential of melanoma cells. In vitro, Gal-3 silencing resulted in loss of tumor cell invasiveness and capacity to form tube-like structures on collagen ("vasculogenic mimicry"). cDNA microarray analysis after Gal-3 silencing revealed that Gal-3 regulates the expression of multiple genes, including endothelial cell markers that appear to be aberrantly expressed in highly aggressive melanoma cells, causing melanoma cell plasticity. These genes included vascular endothelial-cadherin, which plays a pivotal role in vasculogenic mimicry, as well as interleukin-8, fibronectin-1, endothelial differentiation sphingolipid G-protein receptor-1, and matrix metalloproteinase-2. Chromatin immunoprecipitation assays and promoter analyses revealed that Gal-3 silencing resulted in a decrease of vascular endothelial-cadherin and interleukin-8 promoter activities due to enhanced recruitment of transcription factor early growth response-1. Moreover, transient overexpression of early growth response-1 in C8161-c9 cells resulted in a loss of vascular endothelial-cadherin and interleukin-8 promoter activities and protein expression. Thus, Gal-3 plays an essential role during the acquisition of vasculogenic mimicry and angiogenic properties associated with melanoma progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Apoptosis
  • Cadherins / metabolism
  • Cell Line
  • Cell Proliferation
  • Female
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Interleukin-8 / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microvessels / anatomy & histology
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neovascularization, Pathologic*
  • Oligonucleotide Array Sequence Analysis


  • Antigens, CD
  • Cadherins
  • Galectin 3
  • Interleukin-8
  • cadherin 5