eAGR2 promotes cancer metastasis in prostate and pancreatic cancer xenografts. A Loss of ER retention sequence (KTEL) increases levels of eAGR2 in spent media in MiaPaCa-2 cells. B MiaPaCa-2 pancreatic cancer cells carrying luciferase were transfected with GFP, AGR2 wt, and AGR2 ΔKTEL and were injected into left ventricle of (N = 10) nude mice (per arm) to investigate the impact of increased secretion of AGR2 and tumor growth. C Error bars are expressed as average ± SD. Results were normally distributed with equal variance between groups were analyzed by unpaired two-tailed Student’s t test. Asterisks denote p value significance (Student’s t test, p < 0.05) between AGR2 wt and AGR2 ΔKTEL. D Prostate cancer xenografts (N = 10 per arm) were injected with purified recombinant AGR2 by intravenous injection in the left ventricle show increased tumor incidence and E, F with higher flux G, H than control treated mice. Error bars are expressed as average ± SD. Results were normally distributed with equal variance between two groups and were analyzed by paired two-tailed Student’s t test. Asterisks denote p value significance (p < 0.05). i Metastatic spread to right leg (red arrow) but not the left leg (gray arrow) was observed in two mice by CT scan (mouse #195)