Cancer Stem Cells and Pluripotency

Abstract

Determining the functional roles of cancer stem cells (CSCs) and epithelial to mesenchymal transition (EMT) in carcinogenesis and tumorigenesis are pivotal topics in cancer biology research in general and pancreatic cancer in particular. Several publications, including ours, have demonstrated that CSCs and EMT function in tandem, ultimately leading to cancer progression and metastasis [1]. This has been demonstrated in breast, pancreas, and colorectal cancers and likely occurs in all types of cancers. A pressing issue in the field of CSC and EMT research is that of pancreatic adenocarcinoma (PDAC), as it has the worst prognosis of any major malignancy with a 3% 5-year survival rate [2]. Major obstacles in treating pancreatic cancer include delayed diagnosis, extensive local tumor invasion, and early metastasis. CSCs, or cancer initiating cells (CICs), represent approximately 1% to 5% of the tumor, and are capable of unlimited self-renewal, and are often resistant to chemotherapy and radiation therapy [3]. This may explain why these treatments do not cure or prevent recurrence of PDAC [4,5]. Improving survival for all types of cancer likely hinges on the identification and eradication of CSCs. The existence of CSCs was first demonstrated in acute myelogenous leukemia [6] and subsequently verified in breast [7], pancreatic [8], and brain tumors [9-11]. The CD133+ subpopulations from brain tumors can initiate clonally derived neurospheres in vitro showing self-renewal, differentiation, and proliferative characteristics similar to normal brain stem cells [9-11]. In a recent study, a subpopulation of CD44+ CD24+ ESA+ cells derived from primary human pancreatic adenocarcinoma CSCs [8] were implanted in immunocompromised mice and resulted in enhanced tumorigenic potential. We have recently demonstrated that doublecortin and CAM kinase-like-1 (DCAMKL-1) is a pancreatic stem cell marker that is upregulated in pancreatic cancer and may be a marker of CSCs [1,12].