The Glucose Metabolism Reprogramming Of Cancer-associated Fibroblast And Its Impact On ¹⁸F-FDG PET

Objective:Cancer associated fibroblast is an important component of tumor.We aimed to evaluate the glucose metabolism reprogramming of CAF and its influence on the SUVmax of ¹⁸F-FDG PET-CT.Methods:1.We detected the mRNA and protein levels of glycolysis-related genes in NAFs and induced?PDGF and HCT116-CM?CAFs,as well as in isolated NAFs and CAFs,and also between HCT116 and CAF-induced HCT116.2.¹⁸F-FDG uptake was detected by gamma-counter,glucose consumption was detected by GO assay.3.CCK-8 assay was done to evaluate the cytotoxicity of 3-BrP on NAFs and CAFs.4.Micro-PET/CT were done and SUVmax were compared among xenograft models with/without NAFs/CAFs;digital autoradiography were done in AOM/DSS induced-colorectal cancer.5.Colorectal cancer patients with pre-operation ¹⁸F-FDG PET/CT were analysed.6.30 patients were selected,their tumor slices were analysed on IHC of FSP-1 by inform software.The CAF density were compared in two groups.Results:1.The mRNA levels of GLUT-1,HK2 and HIF-1a of CAFs were elevated compared to NAFs as well as the protein levels,the HK2 expression level was elevated in CAF-induced HCT116.2.CAFs uptake more ¹⁸F-FDG and have a higher level of glucose consumption,the ¹⁸F-FDG uptake of CAF-induced HCT116 was reduced.3.CAFs were more sensitive to 3-BrP than NAFs,no matter the concentration of glucose.4.The SUVmax of ¹⁸F-FDG PET in the CAF group was significantly higher than the other two groups.The SUVmax was 1.417±0.083?the CAF group?,compared to 1.067±0.088?the HCT116 group?and 1.067±0.033?the NAF group?,respectively,p<0.05.5.CAFs influence the ¹⁸F-FDG uptake in AOM/DSS induced colorectal cancer tissue.6.In 126 colorectal patients,the SUVmax was only correlated on tumor size.In 30 balanced patients,the CAF density was significantly higher in the SUVmax-high group compared to the SUVmax-low group,2.27±0.74 vs.1.68±0.45,t=2.898,p=0.014.7.The recurrence rate was higher in SUVmax-high group,and we found CAFs infiltration in incision margin.Conclusions:Our data have demonstrated that CAFs are an important cell population closely associated with SUVmax value,which is a useful indicator for prognosis and anti-CAF therapy.