Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling

Abstract

Background: Galectin-1 (Gal-1) expression was positively associated with vasculogenic mimicry (VM) in primary gastric cancer (GC) tissue, and that both Gal-1 expression and VM in GC tissue are indicators of poor prognosis. However, whether Gal-1 promotes VM, and by what mechanismsremains unknown.Methods: To investigate the underlying mechanisms,wound healing assay, proliferation assay, invasion assay, and three-dimensional culture were used to evaluate the invasion, metastasis and promoted VM formation effects of the Gal-1. We monitored the expression level of sociated proteins in GC tissues, cell lines in vitro and nude mice tumorigenicity in vivo by immunohistochemistry and western blot.Results: Gal-1 overexpression significantly promoted the proliferation, invasion, migration, and VM formation of MGC-803 cells. Gal-1 was associated with E-cadherin and vimentin in vitro and in clinical samples. The epithelial-to-mesenchymal transition (EMT) induced in MGC-803 cells by TGF-β1 was accompanied by Gal-1 activation and promotion of VM formation, while knockdown of Gal-1 reduced the response to TGF-β1, suggesting that Gal-1 promotes VM formation by activating EMT signaling. Overexpression of Gal-1 accelerated subcutaneous xenograft growth and facilitated pulmonary metastasis in athymic mice, enhanced the expression of EMT markers, and promoted VM formation in vivo.Conclusion: Our results indicated that Gal-1 promotes VM in GC by upregulating EMT signaling; thus, Gal-1 and this pathway are potential novel targets to treat VM in GC.

Dihydroartemisinin attenuates inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling

“…IHC was performed using lung tissues. Primary antibodies recognizing TGF-β1(dilution, 1:200), JAK2 (dilution, 1:200) , p-JAK2 (dilution, 1:100), STAT3 (dilution, 1:200), or p-STAT3 (dilution, 1:200) were incubated with tissue slides overnight at 4 C, and then processed according to our previous report [35]. All staining was imaged digitally using the same light exposure and evaluated using Image Pro Plus (IPP), a digitalized IHC scoring program (Media Cybernetics, San Diego, CA, USA).…”

Galectin-1 From Cancer-Associated Fibroblasts Promotes the Invasion and Metastasis of Gastric Cancer Through TGF-β1-Induced Epithelial-Mesenchymal Transition

“…Roswell Park Memorial Institute (RPMI) medium (Thermo Fisher Scienti c, Waltham, MA, USA) was used to culture the cells, The culture medium was supplemented with 10% (V/V) fetal bovine serum (FBS; Thermo Fisher Scienti c), 100 U/mL penicillin and 100 mg/mL streptomycin (Gibco, Grand Island, NY, USA). The cells were maintained at 37 °C in a humidi ed atmosphere containing 5% (V/V) CO 2 [24] When con uence reached 80%, the cells were passaged via trypsinization.…”

“…Lentiviral transduction was performed as previously described [24] . Lentiviral vectors for LGALS1 overexpression and silencing were constructed by Genechem Co. Ltd (Shanghai, China).…”

“…Our previous study showed that GAL-1 promoted the invasion, metastasis, and vasculogenic mimicry of GC via EMT [24]. However, the role of TGF-β signaling pathways in GAL-1-mediated promotion of GC EMT remains unclear.…”

Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

“…Maniotis reported that VM was an endothelial-independent vascular channel that contained red blood cells, formed with highly aggressive and metastatic cancer cells in 1999. The structure of VM was a lack of endothelial cells in the internal lining, with CD34 immunohistochemical staining negative/Periodic acid-Schiff (PAS) histochemical staining positive [46]. Furthermore, CSCs possess the highest plasticity and may transdifferentiate to ECs by EMT induction.…”