Galectin-1-driven Upregulation Of SDF-1 In Pancreatic Stellate Cells Promotes Pancreatic Cancer Metastasis

Background:Pancreatic ductal adenocarcinoma(PDAC)continues to be one of the most lethal malignancies with a poor prognosis due to metastasis and local advance.Pathological observation found that there are numerous stromal cells,mainly pancreatic stellate cells(PSCs),around cancer cells in pancreatic cancer microenviroment.As a main component of the tumor stroma,PSCs may participate in the development of pancreatic cancer.In our preliminary studies,Galectin-1 is mainly secreted by pancreatic stellate cells(PSCs).However,very little is known how Galectin-1 modulates PSCs and subsequently impacts pancreatic cancer cells(PCC).Objective:Investigate how Galectin-1 modulates PSCs and subsequently impacts tumor cells metastasis by SDF-1.Methods:We used chemokine antibody array assay testing three primary isolated cancer-associated PSC lines to demonstrate the secretion of chemokines in PSCs after Galectin-1 stimulation.To verify the result,we used lentivirus to silence Galectin-1.QRT-PCR,ELISA and immunofluorescence assaies were conducted to analysis the mechanism.The effect of SDF-1 increasing migration and invasion of PCCs was investigated by transwell assay.SDF-1 neutralizing antibody as well as inhibitor-mediated blockade of its ligand CXCR4 and NF-?B verifies the findings.In vitro by co-culture experiment and in vivo by nude mice pancreatic orthotopic tumor model further demonstrates the conclusion.Results:Galectin-1-driven production of SDF-1 in PSCs through activation of NF-Kb.SDF-1 promotes metastasis in PDAC.Galectin-1 knockdown or blockade of SDF-1/CXCR4 significantly decrease the invasion or migration of cancer cells.In vivo assay,the ability of promoting metastasis was weakened in PSCs after Galectin-1 knockdown as the survival time of the nude vice was prolonged.Conclusion:Collectively,the present studies demonstrate that Galectin-1-driven production of SDF-1 in PSCs through activation of NF-?B promotes metastasis in PDAC.Treatments targeting cancer microenviroment cannot be ignored during comprehensive treatment of PDAC.