Colorectal Cancer Stem Cells

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed and lethal cancers worldwide. It is a multistep process that requires the accumulation of genetic/epigenetic aberrations. There are several issues concerning colorectal carcinogenesis that remain unanswered, such as the cell of origin and the type of cells that propagate the tumor after its initiation. There are two models of carcinogenesis: the stochastic and the cancer stem cell (CSC) model. According to the stochastic model, any kind of cell is capable of initiating and promoting cancer development, whereas the CSC model suggests that tumors are hierarchically organized and only CSCs possess cancer-promoting potential. Moreover, various molecular pathways, such as Wingless/Int (Wnt) and Notch, as well as the complex crosstalk network between microenvironment and CSCs, are involved in CRC. Identification of CSCs remains controversial due to the lack of widely accepted specific molecular markers. CSCs are responsible for tumor relapse, because conventional drugs fail to eliminate the CSC reservoir. Therefore, the design of CSC-targeted interventions is a rational target, which will enhance responsiveness to traditional therapeutic strategies and reduce local recurrence and metastasis. This review discusses the implications of the newly introduced CSC model in CRC, the markers used up to now for CSC identification, and its potential implications in the design of novel therapeutic approaches. STEM

Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass

“…Immunohistochemistry was performed on healthy (n = 27), adenoma (n = 35), including 13 low-grade (mean age at histology examination: 68 ± 14; 7f/6m) and 22 high-grade (mean age: 61 ± 12 years; 14f/8m) dysplasia (according to the description of Fleming et al 40 ) as well as non-metastatic (n = 12; including 3 Dukes A and 9 Dukes B, mean age: 61 ± 5 years; 2f/10m) and metastatic (n = 25; included 14 H&E and immunohistochemistry slides were digitally archived using Pannoramic 250 Flash II (with Zeiss Plan-Apochromat 20x objective; 3DHISTECH, Hungary, Budapest) and Pannoramic Confocal (with Zeiss C-Apochromat 63x objective; 3DHISTECH) digital scanners. Owing to the discrete Musashi1 expression, in the case of ALIX/Musashi1 double staining, we used two step staining and double digitalization as described previously.…”

Cloning and Expression of C2 and V Domains of ALCAM Protein in E. coli BL21 (DE3)

“…ALCAM is considered as a stem cell marker in colorectal [28][29][30][31][32] prostate [33,34] and glioblastoma cancer [35]. Cancer stem cells are a small subset of cancer cells that have considerable ability in selfrenewal and differentiation [36][37][38][39][40][41][42][43][44][45][46][47][48].…”

Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker "LGR5" and the Proliferation Biomarker "TPX2" in Colorectal Carcinoma

“…Mechanisms responsible for the initiation, progression, prognosis and adequate management of CRC have been studied [3] . Two theories of CRC carcinogenesis have been stated; a stochastic model, where any cell has the ability of cancer initiation, promotion and progression and a cancer stem cell (CSC) model, that only produced by transformed CSCs having the ability to self-renewal, abnormally differentiate and form a cancer [4] . Although, CSCs have been incriminated in colon carcinogenesis for several years, the complexity of their detection and isolation is still not precisely In order to detect and remove colon CSCs, a selective biomarker "LGR5 (leucine-rich-repeat-containing G-protein-coupled receptor 5)" might be required.…”

“…Two theories of CRC carcinogenesis have been stated; a stochastic model, where any cell has the ability of cancer initiation, promotion and progression and a cancer stem cell (CSC) model, that only produced by transformed CSCs having the ability to self-renewal, abnormally differentiate and form a cancer [4] . Although, CSCs have been incriminated in colon carcinogenesis for several years, the complexity of their detection and isolation is still not precisely clarified [5] .…”