Role of S128R polymorphism of E-selectin in colon metastasis formation

Riccardo Alessandro, Gregorio Seidita, Anna Maria Flugy, Francesca Damiani, Antonio Russo, Chiara Corrado, Paolo Colomba, Lucia Gullotti, Reinhard Buettner, Loredana Bruno, Giacomo De Leo

Research output: Contribution to journalArticlepeer-review

Abstract

The extravasation of cancer cells is a key step of the metastatic cascade. Polymorphisms in genes encoding adhesion molecules can facilitate metastasis by increasing the strength of interaction between tumor and endothelial cells as well as impacting other properties of cancer cells. We investigated the Ser128Arg (a561c at the nucleotide level) polymorphism in the E-selectin gene in patients with metastatic colon cancer and its functional significance. Genotyping for a561c polymorphism was performed on 172 cancer patients and on an age-matched control population. The colon cancer group was divided into groups with (M+) and without observable metastasis (M-). For in vitro functional assays, Huvec transfected cells expressing wild-type (WT) or the S128R variant of E-selectin were established to study in vitro binding ability and signal transduction processes of T84 colon cancer cell line. Our results demonstrated that the Arginine128 allele was more prevalent in the M+ group than in the M- group or normal controls (p < 0.005; odds ratio, 1.56; 95% confidence interval (CI) 1.16-1.92; p < 0.001, odds ratio = 1.65; CI = 1.24-1.99, respectively). In vitro, S128R E-selectin transfected Huvec cells, supported increased adhesion as well as increased cellular signaling of T84 cancer cells compared to WT E-selectin and mock-transfected Huvec cells. These findings suggest that the E-selectin S128R polymorphism can functionally affect tumor-endothelial interactions as well as motility and signaling properties of neoplastic cells that may modulate the metastatic phenotype.

Original languageEnglish
Pages (from-to)528-535
Number of pages8
JournalInternational Journal of Cancer
Volume121
Issue number3
DOIs
Publication statusPublished - Aug 1 2007

Keywords

  • Cell signaling
  • Colon cancer
  • E-selectin
  • Genetic polymorphisms
  • Metastasis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Role of S128R polymorphism of E-selectin in colon metastasis formation'. Together they form a unique fingerprint.

Cite this