CS has been shown to be increased in several cancer types (21), although little is known about DS, which is produced by DS-epi1 and -2, of which the former is predominant in vivo (16). DS-epi1 is highly expressed in SCC tumors, but in which cells is currently unknown. Immunohistochemical staining showed that DS-epi1 was expressed in normal esophageal epithelium and connective tissue as well as in cancer cells and tumor stroma (Fig. 1A–B). Specificity of the anti-DS-epi1 antibody was ascertained on DS-epi1−/− mouse esophagus (Fig. 1C–D) (16). Epimerase activity was subsequently measured in ESCC biopsies and compared to normal esophageal tissue derived from the same patient. We found that DS epimerase activity was 4-fold upregulated in cancer tissue as compared to normal tissue (Fig. 1E). Increased DS epimerase activity was also found in biopsies from esophageal adenocarcinoma and gastric adenocarcinoma patients (Fig. S1). Consistently, DS-epi1 protein expression was highly upregulated (Fig. 1F). At least three isoforms of DS-epi1 were present in tumor samples, possibly corresponding to differences in N-glycosylated isoforms (22), while in normal tissues, DS-epi1 was below detection level. We thus concluded that functional DS-epi1 is elevated in human ESCC.
