A concise review on the current understanding of pancreatic cancer stem cells

Abstract

Several evidences suggest that a small population of cells known as cancer stem cells (CSCs) or tumor initiating stemlike cells within a tumor is capable of tumor initiation, maintenance and propagation. Recent publications have supported the existence of CSCs in pancreatic tumors. The pancreatic stem/progenitor cells, which express self-renewal markers, are identified to be present in the peribiliary gland. Based on the CSC hypothesis, mutations can lead to the transformation of stem/progenitor cells or differentiated cells into CSCs. The pancreatic CSCs express a wide array of markers such as CD44, CD24, ESA, CD133, c-MET, CXCR4, PD2/Paf1 and ALDH1. The CSCs are isolated based on surface markers or by other methods such as ALDEFLOUR assay or Hoechst 33342 dye exclusion assay. The isolated cells are further characterized by in vitro and in vivo tumorigenic assays. The most important characteristics of CSCs are its ability to self-renew and impart drug resistance towards chemotherapy. Moreover, these distinct cells display alteration of signaling pathways pertaining to CSCs such as Notch, Wnt and Shh to maintain the selfrenewal process. Failure of cancer treatment could be attributed to the therapy resistance exhibited by the CSCs. Metastasis and drug resistance in pancreatic cancer is associated with epithelial to mesenchymal transition (EMT). Furthermore, mucins, the high molecular weight proteins are found to be associated with pancreatic CSCs and EMT. Understanding the underlying molecular pathways that aid in the metastatic and drug resistant nature of these distinct cells will aid in targeting these cells. Overall, this review focuses on the various aspects of pancreatic adult/stem progenitors, CSC hypothesis, its markers, pathways, niche, EMT and novel therapeutic drugs used for the elimination of pancreatic CSCs.

Review on Stem Cell Therapy and their Role in Cancer Treatment

“…This sub-population behaves like stem cells by undergoing either asymmetric or symmetric cell division thereby maintaining its population within the cancer [14].…”

“…SP cells constitute a subpopulation of cancer cells that can efficiently efflux the fluorescent DNA binding dye, Hoechst 33342 and ATP binding cassette transporter [14]. Although the use of Hoechst 33342 dye enables identification of Hoechst-negative CSC SPs, the possible toxicity of the dye may cause side effects during cell sorting [11].…”

“…Although the use of Hoechst 33342 dye enables identification of Hoechst-negative CSC SPs, the possible toxicity of the dye may cause side effects during cell sorting [11]. Small differences in cell densities, dye concentrations and staining timings may affect the phenotype of the SP cells [14].…”

“…ALDH is required for the oxidation of intracellular aldehydes thereby resulting in the oxidation of retinol to retinoic acid [14]. ALDHs belong to the oxido-reductase family, which oxidizes a wide range of endogenous and exogenous aldehydes to their corresponding carboxylic acid [11].…”

“…Cancer stem cells (CSCs) or tumor initiating stem-like cells (TICs) are a small subset of cancer cells which are capable of self-renewal and resist various chemotherapeutic drugs. This sub-population behaves like stem cells by undergoing either asymmetric or symmetric cell division by maintaining its population within the cancer [14]. CSCs and normal tissue stem cells possess selfrenewal capacity; however, self-renewal is typically deregulated in CSCs because CSCs appear to be preferentially endowed with the capacity of self-renewal and responsible for long-term maintenance of tumor growth and progression.…”