Biology and Clinical Applications of Pancreatic Cancer Stem Cells Ethan V. Abel, Diane M. Simeone  Gastroenterology  Volume 144, Issue 6, Pages 1241-1248 (May 2013) DOI: 10.1053/j.gastro.2013.01.072 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Signaling Pathways in PCSCs. The PCSC cell surface markers ESA, CD24, and CD44 likely promote cell–cell or cell–matrix interactions, whereas the receptors CXCR4 and c-Met respond to secreted ligands to promote cancer cell migration, invasion, proliferation, and survival. Developmental pathways, such as β-catenin and Notch, are highly active in PCSCs and could be activated by canonical stimuli or oncogenes, such as ATDC and c-Met. These pathways stimulate the expression of genes that regulate stem-cell properties, such as self-renewal. Oncogenic K-Ras activates expression of SHH, which is secreted by PCSCs and activates surrounding stromal cells. Gastroenterology 2013 144, 1241-1248DOI: (10.1053/j.gastro.2013.01.072) Copyright © 2013 AGA Institute Terms and Conditions

Figure 2 PCSCs and the tumor microenvironment. Primary and metastatic tumors contain a small number of PCSCs, which undergo self-renewal and differentiate into bulk tumor cells. PCSCs can be stimulated to self-renew by growth factors, secreted by either stromal cells or other PCSCs. In turn, PCSCs activate stromal cells by secreting growth factors and SHH. PCSCs can be attracted to sites of metastasis by factors such as SDF-1, produced by distant stromal cells. Finally, PCSCs can resist chemotherapeutic agents to re-establish tumors in patients. Gastroenterology 2013 144, 1241-1248DOI: (10.1053/j.gastro.2013.01.072) Copyright © 2013 AGA Institute Terms and Conditions

Gastroenterology 2013 144, 1241-1248DOI: (10. 1053/j. gastro. 2013. 01 Copyright © 2013 AGA Institute Terms and Conditions

Gastroenterology 2013 144, 1241-1248DOI: (10. 1053/j. gastro. 2013. 01 Copyright © 2013 AGA Institute Terms and Conditions