Role of Cancer Stem Cells in Colitis-Associated Colorectal Cancer

Role of Cancer Stem Cells in Colitis-Associated Colorectal Cancer

Vasudevan Sekar (University of Madras, India)
DOI: 10.4018/978-1-7998-3580-6.ch009
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Colorectal cancer the third-leading cause of cancer mortality Worldwide; it's a well characterised model at molecular level among various cancera. Chronic ulcerative colitis is one of the causes of colorectal cancer. Recent cancer research focuses on tumor-initiating cells which are the cause of tumor initiation, invasions, drug-resistant, recurrence, and metastasis. Emerging research findings support the presence of colon cancer stem cells in sporadic colorectal cancer and in colitis-associated colorectal cancer. Colitis-associated cancer cells exhibit increased colon cancer stem cell marker expression along with activated developmental signaling pathways. Also, emerging reports exhibit that inhibition stem cell markers in chronic ulcerative colitis cells impedes progression of cancer in genetically engineered animal models and primary samples. This chapter deals of colitis-cancer transition, microenvironment of colitis-associated colorectal cancer, and articulates that cancer stem cells are ideal targets for colorectal cancer.
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1. Introduction

Colitis associated colorectal cancer is known as extensive and long-lasting chronic inflammation, the complication of inflammatory bowel diseases with cancer development in colon cancer rectum. Inflammatory bowel diseases are group of chronic inflammation in the gastrointestinal tract, which is caused by an inflammatory response in the gastrointestinal microbiome.(Eaden, Abrams, & Mayberry, 2001; Shacter & Weitzman, 2002) There are two distinct well known inflammatory bowel diseases are Crohn's diseases and ulcerative colitis. Crohn’s diseases will affect anywhere in the gastrointestinal tract from mouth to the anus, mostly dominant in the small intestine. Ulcerative colitis will affect in the colon. Colitis is also known as an inflammation of the colon. Ulcerative colitis is characterised by relapsing and remitting mucosal inflammation from the rectum to proximal colon, resulting in bloody diarrhea, colonic motility dysfunction, and colonic tissue damage.(Al Bakir, Curtius, & Graham, 2018; Romano et al., 2016) Patient with ulcerative colitis are at increased risk of colorectal cancer. Colitis associated colorectal cancer is one of the most serious consequences of ulcerative colitis. In 1925 Crohn and Rosenberg reported the first case of adenocarcinoma in ulcerative colitis patient.(Dobbins, 1984) The major risk factors are the degree of inflammation, diagnosis of young age ulcerative, long duration of ulcerative colitis, family history of Colorectal cancer, accumulation of inflammatory changes associated with colonic epithelial injury, repair, and regeneration.(Beaugerie & Itzkowitz, 2015; Pinczowski, Ekbom, Baron, Yuen, & Adami, 1994; Velayos et al., 2006) Colitis associated-colorectal cancer developed from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma.(Yashiro, 2014) Ulcerative colitis-associated colorectal cancer contributes to 1% of overall colorectal cancer. The incidence of colitis associated-colorectal cancer is ten times greater than sporadic colorectal cancer. Colitis associate-colorectal cancer diagnosed at an advanced stage.(Baars et al., 2011; Gyde et al., 1982) The cancer stem cells theory demonstrates, cancer stem cells are small subpopulation present in the tumour bulk, which possesses the self-renewal and differential capability. Cancer stem cells are causes for tumor initiation, progression, drug resistance and metastasis of cancer. Cancer stem cells are have similar characteristics as normal stem cells.(Bu & Cao, 2012; Dhawan, Ahmad, Srivastava, & Singh, 2011; Zhou et al., 2018) The cancer stem cells were first identified in hematological malignancy and later in solid tumor.(Bonnet & Dick, 1997) The cancer stem cells identified and isolated by using cell surface marker such as CD133, CD24, CD44, CD166, lgr5 etc. also functional markers ALDH and stem cell transcription factors Oct,SOX, Nanog, etc. Colon cancer stem cells were identified using the cell surface markers CD133, CD44, CD166 Lgr5 and ALDH.(Gabriela Pop, 2019; Munro, Wickremesekera, Peng, Tan, & Itinteang, 2018) Based on the cancer stem cells theory, several establish reports exhibits that the cancer stem cells involved in the tissue regeneration and carcinogenesis of sporadic cancer. Where as in ulcerative colitis associated-colorectal cancer, role of cancer stem cells in the inflammation dysplasia carcinoma sequence has not fully understood. In this chapter, its stand to reason that role of cancer stem cells influence in the ulcerative colitis associate-colorectal cancer which may lay a platform for early diagnostic and identification of therapeutic targets.

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