Integrative transcriptome analysis revealed common traits enriched for stemness-associated genes, although each individual CSC gene expression signature exhibited activation of different oncogenic pathways (e.g., EGFR, Talazoparib cost SRC, and MYC). The common CSC
signature was associated with malignant progression, which is enriched in poorly differentiated tumors, and was highly predictive of prognosis in liver and other cancers. Conclusion: Epigenetic modulation may provide a tool for prospective isolation and in-depth analysis of CSC. The liver CSC gene signatures are defined by a pernicious interaction of unique oncogene-specific and common stemness traits. These data should facilitate the identifications of therapeutic tools targeting both unique and common features of CSCs. (HEPATOLOGY 2011;) It is increasingly recognized that many solid tumors contain a subset of cells that possess functional properties ascribed to normal stem cells, such as self-renewal, unlimited proliferative capacity and pluripotency, leading to a hierarchical model of cancer with a cancer stem
cell (CSC) population at the apex of tumor formation.1 The CSC hypothesis posits that CSCs are responsible not only for tumor initiation but also generation of metastasis and local recurrence after therapy.2 The existence of CSCs (also referred to as tumor-initiating cells) has been shown in a variety of solid tumors, including liver cancer.3, 4 However, CSCs have highly variable antigenic and functional properties even when derived from the same tumor NVP-BEZ235 mw type, thus highlighting acetylcholine heterogeneity as a cardinal problem in CSC biology. It is conceivable that the CSC phenotype may be corrupted by distinct oncogenic events and influenced by various factors, including tissue microenvironment, resulting in an assortment of CSCs.5 Therefore, defining both unique and common CSC properties is essential for both understanding CSC biology and effective therapeutic
translation. Currently, most studies focusing on liver CSCs rely on cell surface markers, primarily single markers. This approach identified stem-like cancer cells with clonogenic and tumorigenic capacity, strongly supporting the existence of CSCs in hepatocellular carcinoma (HCC).6-8 Nonetheless, antigenic approaches have several shortcomings, including cross-reactivity, lack of specificity, and antibody-dependent toxicity.9, 10 Furthermore, it has been shown recently that the primary tumor oncogenotypes can influence the marker phenotypes of CSCs, raising questions regarding the use of single markers in molecularly diverse malignancies.5, 11 Alternatively, the side population (SP) approach, which is based on the functional property of CSCs to exclude Hoechst-33342-dye via ABCG2-transporters, might have certain advantages for prospective isolation and characterization of CSCs from liver and other cancers.