Not all pancreatic malignancy cells within a tumour carry the same metastatic potential, and only a small subset of cells home to specific sites in the body
Not all pancreatic malignancy cells within a tumour carry the same metastatic potential, and only a small subset of cells home to specific sites in the body. markers for the recognition of murine malignancy stem cells. Consequently, while the medical relevance of malignancy stem cells remains a fundamental issue for this rapidly growing field, current findings clearly suggest that specific removal of these cells is possible and therapeutically relevant. Focusing on of signalling pathways that are of particular importance for the maintenance and the removal of malignancy stem cell as the proposed root of the tumour may lead to the development of novel treatment regimens for pancreatic malignancy. Here we will review the current literature on pancreatic malignancy stem cells and the future perspective of this rapidly growing field. and tumourigenicity assays. The CSC theory is an intriguing model Madecassic acid to explain both the wide heterogeneity observed in an originally monoclonal tumour, and tumour relapse after treatment due to the presence of a therapy\resistant populace. However, the application of this theory to the development of pancreatic malignancy and the recognition, quantification, and medical relevance of pancreatic malignancy stem cells is definitely a controversial issue. In addition, the cell source of pancreatic malignancy stem cells still remains to be recognized (Hermann et?al., 2009). One probability is definitely that CSCs arise from somatic stem or progenitor cells with genetic alterations that lead to malignant behaviour. Another possibility would be that CSCs originate from the dedifferentiation of a lineage\committed cell that has (re\)acquired stem cell characteristics through mutation. This problem is further complicated by the current lack of convincing evidence for a stable stem cell populace in the normal pancreas. The recognition and precise investigation of a putative pancreatic stem cell including its market using genetically designed mouse models (GEMM) will hopefully add further insights to understand the origin of CSCs. 3.?Pancreatic cancer stem cell markers and heterogeneity of pancreatic cancer cells Putative pancreatic CSCs, for the first time defined from the simultaneous expression of CD44, CD24, and EpCAM (Li et?al., 2007), are highly tumourigenic and possess the ability to both self\renew and to produce differentiated progeny that displays the heterogeneity of the patient’s main tumour. However, it should be mentioned that with this 1st study, putative CSCs were compared to a populace of cells that were negative for those three markers. Since EpCAM identifies epithelial cells within the tumour, Madecassic acid the confinement to EpCAM bad cells as the control populace may have been too restrictive, as these cells should primarily represent non\epithelial inflammatory, stromal and vascular cells (Li et?al., 2007). Using a different cell surface marker, Hermann et?al. showed that CD133+ cells in main pancreatic cancers and pancreatic malignancy cell lines also discriminated cells with enhanced proliferative capacity (Hermann et?al., 2007), which also show the defining CSC characteristics. Interestingly, they showed that this CD44+CD24+EpCAM+ subpopulation clearly overlaps with the CD133+ populace. In a more recent study, Mueller et?al. also used CD133 to investigate for the first time a therapeutic strategy targeting this subpopulation of Madecassic acid human pancreatic cancer cells that is highly enriched for tumour\promoting CSCs both in primary pancreatic cancer cells and the xenografted pancreatic cancer cell line L3.6pl (Mueller et?al., 2009). Other distinctive markers have also been used for the characterization of CSCs: ALDH\1 (ALdehyde DeHydrogenase\1) has been shown to be associated with the tumourigenic cells in pancreatic cancer (Feldmann et?al., 2007; Jimeno et?al., 2009; Rasheed et?al.), although more recent comprehensive investigations suggest an abundant expression of ALDH\1 in normal pancreas tissue (Deng et?al.), which would disqualify ALDH\1 as a suitable marker for CSCs in humans. Moreover, side populace (SP) cells, which exclude the DNA dye Hoechst 33342, proved to be malignancy\initiating cells in several tumours (Hirschmann\Jax et?al., 2004), but these data require further validation as the use of SP cells in gastrointestinal cancers has generated conflicting data (Burkert et?al., 2008). Apparently, a number of studies have published conflicting data around the expression of these markers for the Madecassic acid identification of pancreatic CSCs, particularly for CD133, suggesting that this analyzed CSC populations are by no means real and technical obstacles still remain. Importantly, it was reported that the use of different CD133 antibodies can translate into significantly different findings (Mueller NRAS et?al., 2009). Two studies using different CD133 antibodies for histological analysis on pancreatic cancer tissue have led to opposing results with respect to the CD133 expression patterns (Immervoll et?al., 2008; Maeda et?al., 2008). Moreover,.