INS and exocrine pancreatic carcinoma: Based on the above observations, preferential expression of heparanase in PDAC tumors (Koliopanos et al., 2001; Rohloff et al., 2002; Quiros et al., 2006; Hoffmann et al., 2008), and the presumed role of excessive insulin signaling in pancreatic tumorigenesis (Chan et al., 2014; Zhang et al., 2019; Deng et al., 2022), we hypothesized that the enzyme can also augment INSR signaling in pancreatic carcinoma cells, thus promoting PDAC progression.