Pancreatic cancer cells secrete a large number of paracrine cytokines, as summarized in Table 1, such as transforming growth factor-beta (TGF-β), Sonic hedgehog (Shh), and Interleukin-1 (IL-1) alpha to activate PSC (Sherman, 2018), while direct contact between pancreatic cancer cells and PSC, stimulating the Notch signaling pathway in PSC, leads to the activation of PSC (Fujita et al., 2009). Here, SHH is linked to familial pancreatic carcinoma.