Heterogeneity of Colon Cancer Stem Cells
Colorectal cancer (CRC) remains the fourth leading cause of cancer death worldwide. Cancer stem cells (CSCs) have attracted a great deal of interest because of their potential clinical implications in a range of cancers, including CRC. CSCs were initially
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Heterogeneity of Colon Cancer Stem Cells Akihiro Hirata, Yuichiro Hatano, Masayuki Niwa, Akira Hara, and Hiroyuki Tomita
Abstract Colorectal cancer (CRC) remains the fourth leading cause of cancer death worldwide. Cancer stem cells (CSCs) have attracted a great deal of interest because of their potential clinical implications in a range of cancers, including CRC. CSCs were initially considered to be cell populations with well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent a phenotypically and functionally heterogeneous population. Recent studies also demonstrate colorectal CSCs to be dynamic rather than static populations that are continuously altered by various extrinsic factors in addition to intrinsic cellular factors such as genetic and epigenetic alterations. Thus, CSCs do not represent a fixed target population any longer, and their heterogeneous and dynamic nature present a serious problem in establishing specific therapeutic strategies. This chapter summarizes past and current literature related to CSC population heterogeneity and dynamics in CRC tissues, including evidence of the presence of distinct CSC subpopulations and signaling pathways and intra- and extra-tumoral factors involved in the regulation of CSCs in cancer tissues. Keywords Colorectal cancer · Cancer stem cell · Heterogneity · Cancer stem cell marker · Metastasis · Wnt signaling · Intestinal stem cell · Reversion · Plasticity · Tumor microenvironment
A. Hirata Division of Animal Experiment, Life Science Research Center, Gifu University, Gifu City, Gifu, Japan e-mail: [email protected] Y. Hatano · A. Hara · H. Tomita (*) Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu City, Gifu, Japan e-mail: [email protected]; [email protected]; [email protected] M. Niwa Medical Science Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu City, Gifu, Japan e-mail: [email protected] © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_7
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It has long been recognized that malignant cells within the same tumor display significant heterogeneity with regards to morphology, proliferative activity, and function (Heppner and Miller 1983). The cancer stem cell (CSC) concept can provide a convincing explanation of the mechanism underlying cellular heterogeneity within tumors. CSCs, also called tumor-initiating cells, are defined by their capacity to self-renew and generate diverse cells that comprise the tumor (Kreso and Dick 2014), and are thought to initiate and continually sustain tumor growth. The first evidence for the existence of CSCs came from studies on acute myelogenous leukemia (AML) in the 1990s, where a rare subset with the CD34+/CD38− phenotype could induce leukemia in immunocompromised mice (Bonnet and Dick 1997; Lapidot et al. 19
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