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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Several surface makers which expressing from mesenchymal stem cells. Basically, these makers are the cell receptors, adhesion molecules, extracellular matrix proteins, cytokines and other molecules that have function as a way of communicating with other cells and to carry out their physiological functions. Thus, these makers are adopted to characterize the homogenous mesenchymal stem cells. However, the Bone marrow-derived stem cells expression of different surface markers which are still controversy. These cells have a negative expression of CD45 which express in Hematopoietic stem cell (HSC) (McKinney-Freeman et al., 2009), CD14 which express in innate immune cells (Cros et al.
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Stem cells offer the capability to develop into many different cell types in the body in the time of early life and growth. Furthermore, in many cell tissues they serve as an internal repair system, dividing almost without
However, they are identified in people with colon cancer. The most abundant bacteria in our gut and causing cancer are Proteobacteria, Firmicutes and Bacteroidetes. When colon tumor genes are analyzing, alterations in these genes are founded. APC and CTNNB1, P53 genes have deletions in people with colon cancer. In addition, DNA methylation at CpG islands are abnormal, and chromosomes are instable. All these DNA alterations mentioned due colon cancer are mentioned to occur in the stem cells in the base of the villus crypt. The crypt is occupied by a numerous of differentiated cells, which renew to generate epithelium after an injury. Bacteria induced DNA alteration, E. Coli downregulate DNA mismatch repair protein, so this mechanism enhance tumor formation. In the case of, Enteroccous faecalis produce aneuploidy in the epithelial cells, aneuploidy is an abnormal number of chromosomes in a cell. Overall, there are many factors undelaying colon cancer that need to be studied. However, formation of cancer in the colon can take place due to reduction of protective bacteria, changes in energy uptake and metabolic disorders. For future considerations, it is important to understand the place that take the
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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.
Over time there has been the discovery of many different type of cancer, which all begins in cells, that can be classified as a body’s form of basic building blocks. Cancer cells are essentially cells that have gone wrong, meaning they no longer generate responses to the signals, which control the human cellular developments. Cancer cells have a complex nature, due to its combination of various abnormalities that results in normal cells becoming cancer cells. Over time, cancel cells are developed within tissues and, as the tissues grow the cells grow and divide, resulting in the cells becoming resistant towards the signals that maintain the normal tissue production. In the final stages of cancer, the cancer cells are capable of breaking through normal tissue boundaries and metastasizing throughout the body.
The Authors, members of the Curtis Lab at Stanford University, propose and justify the Big Bang model for colorectal tumor growth. This model is dependent on several characteristics found in samples including the absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions. The model concludes that mutations occurring early in the tumor development will have a larger effect on overall tumor composition compared to later mutations in spite of the fitness advantages presented by either mutation. This model also provides a possible biomarker for determination of malignant vs benign phenotypes from the primordial tumor. Carcinomas were
Increasing experimental evidence supports the cancer stem cell model in HNSCC, which is in favor of a small proportion of cells with the capability of sustaining tumour formation and growth, self-renewal and differentiation in a tumour type and context dependent manner. These CSCs have a probable role in resistance to therapy, establishment of metastasis and recurrence which is allusive of the fact that targeted elimination of th...
“Stem Cells: The Future of Medicine.” Medschool.umaryland.edu. University of Maryland School of Medicine Web 14 Nov 2013
There have been extraordinary progresses in identifying cancer at the cellular level and the question of how cancer cells develop are no longer a secret. Although there are many different types of cancer and almost every tissue can turn into malignancies, the basic processes of how cancer arises are very similar. While normal body cells follow the orderly path of cell cycle and only reproduce when instructed to do so, cancer cells violate the schedule and ignore instructions, it fails to follow the orderly enzymatic reaction which is responsible for the deletion of cells with damaged DNA (Kerr et al. 1994). Cancer cells enter cell cycle repeatedly until it will eventually disrupt the function of tissues and organs that are essential to the organism (Weinberg 1996). Not all types of cancer are fatal, benign cancer is a type of cancer which stays in one location only, in another word it will not m...
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)
BE (colon carcinoma), LS174T (colon carcinoma), SW962 (squamous cell carcinoma), WM266.4 (melanoma), A375P, and A375m2(melanoma) cells were analyzed to test for cell invasion relative to the controls used.
Consequently, chronic UC patients have an increased risk of developing colorectal cancer (CRC). There are no truly effective treatments for UC at the present. Accordingly, the risk of developing CRC remains high. Thus, the development of novel treatment approaches for this disorder is required to attenuate the inflammatory response, prevent mucosal damage and facilitate mucosal healing (Abimosleh et al, 2012).