| Endometrial cancer(EC)is the most common gynecologic cancers in the developed countries,With changes in Western lifestyle,concept of fertility and hormone use in our country,the incidence of EC has steadily risen in recent years.The carcinogenesis of EC has targeted the tumor cells for a long time.The tumor is often portrayed as an evolutionary process involving autonomous growth among tumor cells without regulation.This theory emphasizes the role the tumor cells,while ignoring the tumor microenvironment interactions between tumor cells.The TME is composed of tumor cells,stromal cells,numerous soluble molecules such as growth factors,cytokines,chemokines,proteases,and metabolites as well as a extracellular matrix.It is known as a local pathological condition that played a major role in tumor initiation,growth and metastasis.The stromal cells are composed of endothelial cells,fibroblasts,lymphocytes and macrophages.Cancer-associated fibroblasts(CAFs)are one of the most important and abundant stromal cells,played "passive" roles to support and nutritional epithelial cells in the past.But recent studies have found thatCAFs palys "active" roles in the regulation of homeostasis in the tumor environment,or even determine the fate of epithelial cells.CAFs can secrets a number of cytokines,SDF-1 and SDF-1/CXCR4 biological axis in the tumor environment were drew more attention.Research about CAFs promotes tumor growth were more studied in breast cancer,lung cancer and prostate cancer currently,little known in EC.Therefore this study from the perspective of the tumor microenvironment to explore the progression and the mechanism of EC.Objetive:We aim to explore the role of CAFs in the biological behavior of EC in vitro and vivo experiments;The detection of the secretion levels of SDF-1 by CAFs in EC;To determine whether SDF-1 can promote EC cells growth,migration and invasion.Methods:The effect of CAFs/NFs promote ECC-1 and HEC-1B cell proliferation,migration and invasion was measured by MTT assay and Transwell chamber in vitro.CAFs/NFs and EC cells were inoculated to nude mice in accordance with the mixing ratio of 1:3(total number of cells is 80×106).Observed the tumor formation time,the rate of formation tumor,the rate of lymph node metastasis,the tumor mass and the tumor volume.Elisa assay was used to measured the levels of SDF-la in the supernatant of CAFs/NFs.The effect of SDF-1α and CXCR4 antagonist AMD3100 on ECC-1 and HEC-1B cells proliferation,migration and invasion were measured by MTT assay and Transwell chamber in vitro.The effect of SDF-la and AMD3100 promote ECC-1 and HEC-1B cells expressing MMPs were measured by gelatin zymography.Results:(1)CAFs/NFs and EC cells were mixed at the ratio of 1:3 reached a peak proliferation at 72 hours(P<0.05),The effect of promoting proliferation in CAFs is significantly increased than NFs’(P<0.05).(2)CAFs promote EC cells migration and invasion were significantly increased when compared with NFs(P<0.05).(3)CAFs group and NFs group showed no lymph node metastasis,100%of tumor formation rate.(4)The tumor formation time,the tumor mass and the growth rate of CAFs group were signifinantly short than NFs group and control group(P<0.05).(5)The level of SDF-la was secreted by CAFs group were increased sifnificantly when compared to NFs group(P<0.05).(6)The concentration of SDF-la is more than 200ng/ml enhanced the ablity of proliferation,migration and invasion in EC cells(P<0.05);The concentration of AMD3100 is more than 500ng/ml can block the effect of SDF-la on proliferation,migration and invasion in EC cells(P<0.05).(7)The concentration of SDF-la is more than 200ng/ml can promote the expression of MMP2 and MMP9 in EC cells(P<0.05);The concentration of AMD3100 is more than 500ng/ml can block the effect of SDF-la on expression of MMP2 and MMP9 in EC cells(P<0.05).Conclusions:The secretion level of SDF-la were increased by CAFs in EC,SDF-la can promote EC cells proliferation,migration,invasion and expression of MMP2 and MMP9 through SDF-1/CXCR4 biological axis. |
PDF Full Text Request