Pancreatic Cancer Stem Cells

Various levels of evidence suggest that a small population of tumor cells known as cancer stem cells (CSCs) or tumor initiating stem like cells initiate and maintain tumors. CSCs have been identified in pancreatic cancer ductal adenocarcinomas (PDAC) and are known to self-renew and propagate the parental tumor. The lack of early symptoms, extensive metastasis and high resistance to chemotherapy and radiation render pancreatic cancer the fourth most common cause of cancer related death. Tumor initiating/propagating cells express cell surface markers such as CD133 and CD44 and show features of epithelial-mesenchymal transition (EMT) resulting in metastasis. In addition, densely glycosylated proteins known as mucins are found to be associated with pancreatic CSCs and play a role in EMT. Typically, activating mutations in the Kras2 gene are detected in pancreatic tumors accompanied by inactivating mutations in tumor suppressor genes such as Arf or P53. The cell-of-origin of PDAC is still unknown, as both exocrine and endocrine cells can initiate tumors during chronic inflammation. Future studies investigating pancreatic stem cells and progenitor cells in more detail will help identify more precisely the cell-of-origin of PDAC. Understanding the underlying molecular pathways of the metastatic and drug resistant nature of these distinct cells will open up new avenues in targeting these cells. The highly heterogeneous pancreatic CSC pool is more resistant to standard chemotherapy than the more differentiated tumor cells, and therefore, strategies to specifically target PDAC CSCs will provide new therapeutic prospects for this devastating disease.