title: Role of S128R polymorphism of E-selectin in colon metastasis formation.
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 Arginine(128) 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.
authors: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Palermo, Italy. ricale@unipa.it
authors: Riccardo
authors: R
authors: Alessandro
authors: Gregorio
authors: G
authors: Seidita
authors: Anna Maria
authors: AM
authors: Flugy
authors: Francesca
authors: F
authors: Damiani
authors: Antonio
authors: A
authors: Russo
authors: Chiara
authors: C
authors: Corrado
authors: Paolo
authors: P
authors: Colomba
authors: Lucia
authors: L
authors: Gullotti
authors: Reinhard
authors: R
authors: Buettner
authors: Loredana
authors: L
authors: Bruno
authors: Giacomo
authors: G
authors: De Leo
mesh_terms: D001120:Arginine; D002448:Cell Adhesion; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012694:Serine; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D019040:E-Selectin; D012694:Serine; D001120:Arginine