An invited review following the Soujinkai Young Investigator Award : calreticulin is highly expressed in pancreatic cancer stem-like cells

Pancreatic cancer is an intractable disease with a poor prognosis. Recent research has demonstrated that the resistance of these cancers to conventional treatment, the high rate of local recurrence and distant metastasis may be attributed to a small subset of cells in cancer tissues known as cancer stem-like cells. It is critically important to elucidate the biological properties of cancer stem-like cells and develop strategies targeting these cells to overcome pancreatic cancers. We established a pancreatic cancer stem-like cell induction method from a cancer cell line and identified calreticulin as a highly expressed protein on the surface of these cells using proteomics and flow cytometry. Notably, we demonstrated that calreticulin was expressed on cells with high ATP-binding cassette transporter activity known to mediate drug efflux and related to poor outcomes in pancreatic cancer patients who underwent curative resection. Calreticulin exposure in cancer stem-like cells could be regulated by oxidative stress via hypoxia-inducible factors which induce the expression of CD47 and PD-L1 to evade the immune-surveillance of these cells. Further investigations on calreticulin expression in pancreatic cancer stem-like cells could elucidate the pathophysiology of these cells, leading to the development of novel therapy.

pancreatic cancer

cancer stem-like cells

calreticulin