Role of Cancer Stem Cells in Colitis-Associated Colorectal Cancer

Author(s):  
Vasudevan Sekar

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.

2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014


2019 ◽  
Vol 156 (3) ◽  
pp. 708-721.e15 ◽  
Author(s):  
Fang Hua ◽  
Shuang Shang ◽  
Yu-wei Yang ◽  
Hai-zeng Zhang ◽  
Tian-lei Xu ◽  
...  

2020 ◽  
Vol 19 ◽  
pp. 153303381989226
Author(s):  
Yu-Shui Ma ◽  
Wen Li ◽  
Yu Liu ◽  
Yi Shi ◽  
Qin-Lu Lin ◽  
...  

As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4124-4124
Author(s):  
T. Yeung ◽  
J. Wilding ◽  
W. Bodmer

4124 Background: Cancer stem cells are defined as cells within a tumour that are able to self-renew and differentiate into all cell lineages within that tumour. With our extensive panel of colorectal cell lines, our aims are: 1) To characterise and isolate cancer stem cells based on stem cell markers, morphological appearances and the ability to form multiple lineages; 2) To understand how cancer stem cells drive tumour growth and progression. Methods: 1) Fluorescent Activated Cell Sorting (FACS); 2) In vitro soft agar clonogenic and Matrigel differentiation assays; 3) In vivo tumourigenic NOD/SCID mice assay; 4) Confocal immunofluorescence imaging. Results: 1) A subpopulation of cells can differentiate into crypt-like megacolonies, retaining the ability to self-renew and differentiate. SW1222 cell line forms heterogeneous colonies when single cells are plated in Matrigel. Megacolonies can both self-renew and form terminally differentiated small colonies, whereas small colonies cannot form megacolonies. Megacolonies develop crypt-like structures and increase their expression of differentiation markers (CDX-1, CK-20) over time. Experiments are currently under way to confirm that cells from megacolonies are able to initiate tumours in NOD/SCID mice. Some cell lines retain the ability to differentiate into both neuroendocrine and epithelial lineages. 2) CD44+CD24+ enriches for the cancer stem cell population. Colorectal cancer cell lines HCT116, HT29, LS180, LS174T and SW1222 express both CD44 and CD24. The CD44+CD24+ subpopulation is the most clonogenic. In SW1222, CD44+CD24+ cells enrich for megacolonies and can reform all four CD44/CD24 subpopulations. 3) Hypoxia reduces differentiation, increases stem-like phenotype and enhances clonogenicity. Hypoxia increases the proportion of undifferentiated colorectal cancer cells when plated on Matrigel and increases clonogenicity. Conclusions: 1) Colorectal cancer cell lines contain subpopulations of cells that have the ability to self-renew, differentiate and drive tumour growth, and may be characterised by their cell surface markers and colony morphology. 2) CD44+CD24+ can be used as markers for colorectal cancer stem cells. 3) Hypoxia increases the stem-like phenotype of cancer cells, reduces differentiation and increases clonogenicity. No significant financial relationships to disclose.


2019 ◽  
Vol 14 (5) ◽  
pp. 398-404 ◽  
Author(s):  
Iván Flores-Ramírez ◽  
Noemi Baranda-Avila ◽  
Elizabeth Langley

Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells that express stem cell-associated markers. In recent years, their properties and mechanisms of regulation have become the focus of intense research due to their intrinsic resistance to conventional cancer therapies. This review describes breast cancer stem cell origin, signaling pathways involved in self-renewal, such as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex steroid hormones in BCSC regulation.


2011 ◽  
Vol 8 (5) ◽  
pp. 511-524 ◽  
Author(s):  
Anna Merlos-Suárez ◽  
Francisco M. Barriga ◽  
Peter Jung ◽  
Mar Iglesias ◽  
María Virtudes Céspedes ◽  
...  

2021 ◽  
Vol 18 (2) ◽  
pp. 171-183
Author(s):  
Alicja Zalewski ◽  
Adam E Snook ◽  
Scott A Waldman

Colorectal cancer continues to represent a significant burden on public health as the second highest cause of cancer mortality, when men and women are combined, in the US. About 50% of patients either present with late-stage metastatic disease, or develop metastatic recurrences, and ultimately die. In turn, this mortality largely reflects cancer stem cells, tumor-initiating cells that are responsible for cancer progression, drug resistance, recurrence and metastasis. This review summarizes the unique properties of colorectal cancer stem cells, and the emerging strategies by which they can be selectively targeted as a therapeutic approach to eradicating this disease.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS3650-TPS3650 ◽  
Author(s):  
Edward H. Lin ◽  
Shilpen A. Patel ◽  
Jeffrey Chou ◽  
Edward Y. Kim ◽  
Veena Shankaran ◽  
...  

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