Syndecan-2 expression in colorectal cancer-derived HT-29 M6 epithelial cells induces a migratory phenotype.
Members of the heparan sulfate proteoglycan family, the syndecans have emerged as integrators of extracellular signals, such as ECM components or growth factors, that activate cytoplasmic signaling cascades and regulate cytoskeletal functions. Specifically, syndecan-2 has been implicated in various cellular processes, from differentiation to migration, including its participation in cell-cell and cell-matrix adhesion. Here, we focused on the involvement of syndecan-2 in epithelial versus mesenchymal differentiation. Colorectal cancer-derived HT-29 M6 epithelial cells were stably transfected with full-length syndecan-2 cDNA, and the effect on cell morphology, adhesion, and mobility was evaluated. Characteristic features of migratory cells such as loss of intercellular contacts, flatter shape and multiple membrane projections were observed in syndecan-2 transfectants. Western blot analysis of the major component of epithelial adherens junctions, E-cadherin, revealed decreased expression levels. Furthermore, syndecan-2 induced stronger adhesion to collagen type I, specifically inhibited by heparin. This was correlated with an increased ability for migration, as demonstrated by wound healing experiments and transwell assays, without affecting their growth rate. These results indicate that syndecan-2 expression in mucus-secreting HT-29 M6 cells induces differentiation toward a migratory mesenchymal-like phenotype.
Contreras
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HR
Physiology and Biophysical Program, ICBM, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile.
Fabre
M
M
Granés
F
F
Casaroli-Marano
R
R
Rocamora
N
N
Herreros
A G
AG
Reina
M
M
Vilaró
S
S
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D019073:HT29 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D053669:Syndecan-2; D014162:Transfection; D014945:Wound Healing
D015820:Cadherins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508245:SDC2 protein, human; D053669:Syndecan-2