Summary:
Background and objective. Tumor heterogeneity is shown to be related to clinical outcome in cancer patients. The concept of a small subset of cancer stem cells being responsible for tumor relapse and metastasis comes out as a promising strategy for targeted cancer therapy. However, cancer stem cells are not easy to identify and isolate. The aim of this study was to determine the putative colon cancer stem cell subsets in human colon cancer cell lines HCT116 and HT29, which differ in their aggressiveness and differentiation capacity. Material and methods. Flow cytometry was used to asses HCT116 and HT29 cell lines for the expression of stemness-associated surface markers CD24, CD44, CD117, CD133, ESA, ABCB1. Both cell lines were treated with 5-fluoruracil and the phenotype of chemoresistant cells was investigated. Side population was visualized via Rhodamine 123 staining. Relative expression of ABCG2, c-Myc and Oct4 genes was quantified using qPCR analysis. Results and conclusions. It was shown that HCT116 and HT29 cell lines differ in their stemness-related properties. We imply that putative CSC subset for HCT116 cell line is CD44+/CD24-/CD133- (4,1% of all cells) and for HT29 cells – CD24+/CD44-/CD133- (4,9% of all cells).
Keywords: tumor heterogeneity, colon cancer, cancer stem cells, HCT116, HT29
Introduction
The concept of tumor heterogeneity being related to the course of the disease and clinical outcome in cancer patients draws additional attention in the era of personalized medicine (1). Current cancer treatment strategies are based on the site of origin of the primary tumor. However, it was shown that tumors developed from distinct cell types differ in their prognosis and response to cytotoxic therapies (2...
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In this experiment, both BALB/c and C3H mice are induced with azoxymethane (AOM) and dextran sodium sulphate (DSS). The inflammation is caused by the administration of dextran sodium sulphate to the drinking water of the mice. While azoxymethane induction plays a role in the development to colon cancer. In this project, the development of colon cancer through the inflammation pathway is being researched. The process first starts with the of inflammation foci. Over time, it develops into hyperplasia due to the increasing capacity of cell proliferation.
The cancer stem cell theory hypothesizes that tumors or cancers arise from mutations or epigenetic changes in normal stem cells. These mutated or genetically altered stem cells possess the properties of the normal stem cells such as the ability to self-renew, differentiate into any type of body cell, and resist apoptosis. Hence, the cancer stem cells (CSC) are named so. It is also suggested that because of the above-mentioned properties of the cancer stem cells, the current anti-cancer therapies are not entirely successful (Gil et al, 2008). Despite surgery and other therapies, even if very few of these cancer stem cells survive, they can continue to act as a source for more tumors, even though the therapies eliminate all visible signs of cancer.
Stem Cells: What, How and Why? Stem cells are infinitely valuable when considering their potential applications in the medical profession. While current legislative restrictions have halted the development of new ?stem cell lines? to any agency or company that receives any form of governmental grants, there is no question that the medical profession is standing at the brink of a new era of technological advancements in healthcare and research.
The importance of embryonic stem cells rests in their lack of specialization. These basic cells are present in the earliest stages of developing embryos and are able to develop into virtually any type of cell and tissue in the body. Being self-renewing, they offer a potentially limitless source of cells and tissue. (Tucker)
Wang, K., Wu, X., & Huang, J. (2013, February 28). Cancer stem cell theory: therapeutic implications for nanomedicine. Retrieved December 12, 2013, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589204/
There are many different types of stem cells that are being looked at for research. These include embryonic stem cells, adult stem cells, and induced pluripotent cells. Embryonic stem cells are cells that have the potential to produce many different cells in the body. They are cells that are tak...
“Stem Cells: The Future of Medicine.” Medschool.umaryland.edu. University of Maryland School of Medicine Web 14 Nov 2013
Colon cancer develops in the part of the gastrointestinal tract that absorbs water and minerals before waste products are disposed via the rectum. In women endometrial cancer is related to colon cancer. This type of cancer is the second leading cause of death due to cancer in the United States. Over one-hundred fifty thousand individuals will be diagnosed this year and this cancer will probably be responsible for about 47,900 deaths in 1999 (http://www.cancer.org). Most colon cancers are adenocarcinomas that develop from the glandular cells. Ninety percent of all colon cancer cases will develop in individuals after 50 years of age. Ninety percent of all tumors arise from polyps that are commonly found in people older than 50. Prevention includes regular exercise and a diet high in fiber. The most important risk factor is age. Medical screening includes a yearly blood occult test after age 50 and a colonoscopy every 3 years after age 50. Regular screening detects polyps that have become precancerous. If regular screening is not done, the cancer is not detected until blood is found in the...
In most cases, it's not clear what causes colon cancer. Doctors know that colon cancer happens when healthy cells in the colon become changed.
Over 95% of colorectal cancers are ad enocarcinomas. These are cancers of the glandular cells that line the inside of the colon and rectum. Other, less common type of tumors may also develop in the colon and rectum. Carcinoid tumors develop from hormone-producing cells of the intestine. Gastrointestinal stromal tumors develop in the connective tissue and muscle layers in the wall of the colon and rectum. Lymphomas are cancers of immune system cells that typically develop in lymph nodes but may also start in the colon and rectum or other organs.
This defines these specific stem cells as cells that are capable of regenerating cells in bone marrow and express cell surface markers. Mesenchymal stem cells positively express hematopoietic cell surface markers CD105, CD73, and CD90 and are absent for the expression of CD34, CD45, CD11a, CD19, and HLA-DR (Salem & Thiemermann, 2010). In a study, a patient with sickle cell anemia, was given increased amounts of CD34+ cells that coexpressed the gene gylcophorin A (Luck & Zeng, 2004). The hematopoietic cell surface marker, CD34+ expressing gylcophorin A, helped increase the production of red blood cells. (Luck & Zeng,
Upon castration basal cells are not removed and they are capable of regenerating an intact prostate again under normal androgen levels. Hence these cells are attributed a stem like property. (47-48) prostate cancer stem cells (PrCSC) are subset of cells that have gained interest over the past years because of their self renewal capacity and proliferation. These cells posses set of markers called the stem cells markers that include CD133 , CD 14 and integrin α2β1. (49)
Cancer develops when cells in a part of the body begin to grow out of
Stem cells are a key component of regenerative medicine. They are undeveloped cells capable of proliferation, self renewal, conversion to differentiated cells, and regenerating tissues. [1] In a developing
Blood and urine based biomarkers used in molecular pathology are only indicative of the average response of the cell population affected with little or no information of the range of response or variability form areas of tissue (Naddler and Langley 2001)