It has been shown in different tumors, including pancreatic cancers, that HA in the tumor stroma interacts with a variety of receptors including CD44 and triggers the activation of cancer stem cell markers such as OCT4, Nanog, and Stat-3, as well as a diverse range of growth factors and cytokines, which promote cancer stem cells renewal and expansion, chemoresistance, and an enhanced tumor relapse as a consequence [6,7,13,31,54]. This evidence concerns the gene CD44 and familial pancreatic carcinoma.