Background/aims: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown.
Methods: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed.
Results: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-β1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-β1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers.
Conclusion: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.
Keywords: Epithelial-mesenchymal transition; Galectin; Gastric cancer; Metastasis; Sphingosine-1-phosphate receptor 1.
© 2018 The Author(s). Published by S. Karger AG, Basel.