Carcinogenesis and Its Prevention - Assignment Example

CARCINOGENESIS AND ITS PREVENTION of Table of Contents Table of Contents 2 Question 1: Critically Discuss the Role and Molecular Mechanisms of Cancer Stem Cells in Carcinogenesis 3 Introduction 3 Stem Cells and their Functioning 3 Diagram illustrating the SCs divisional activities 5 Experimental Explanations 6 The Cancer Stem Cell (CSC) Theory 7 Summary 8 References 9 Question 1: Critically Discuss the Role and Molecular Mechanisms of Cancer Stem Cells in Carcinogenesis Introduction Cancer is a form of mutation and epigenetic modifications that affect the genetic composition of individuals causing cell impairment (Trosko, Chang and Madhukar, 2000, p.261). The complexity of carcinogenesis has been tackled by many doctors as they try to ascertain its origins, causal factors and how the process manifests itself. As a result, it has been found that the interplay of factors such as genetic, environmental and age unite and create conditions which facilitate the development of cancer. This is marked by the capability of cells to grow inappropriately, lack cell elimination, microenvironment stimulation, requiring support and finally spreading to other body parts. These new acquired capabilities are regulated by processes such as gene expression through chromatin structure control, damage of fatty-acid metabolism, hormonal exposure, DNA damage and alteration of cell-interactions (Reya, et al, 2001, p.507). The formation of cancer cells continues to replicate causing further mutations which finally lead to complete neoplastic phenotype. Stem Cells and their Functioning To understand this whole process let us first consider stem cells and their role in the body. According to Sell (2003, p.16), mature stem cells are present in many body tissues where they facilitate tissue development, repair as well as replacement when necessary. All these cells have similar characteristics that enable them to replicate through a process of self renewal as they also differentiate to form various tissues in the body. These processes are natural and occur in every normal functioning organism’s body, any alteration of the process may be the key to the development of cancerous tumors. Different theories have been put forth to explain the development of these cancerous tumors, each theory focuses on specific aspects of cancer. For instance, the theory of Cancer Stem-Cell (CSC) explains that the normal stem cell differentiation process when altered forms cells which are terminally differentiated which in turn cause mutation accumulation causing tumor (Trosko, 2004, p.211). At the beginning of the 20th century, people had no explanations on the exact causation of cancer cells. Chang, et al, (2001, p.206) explains that the initial belief was that chemicals were among the causes of cancer with neither particular understanding of the molecules that caused cancer nor their target cells. What was lacking at this time was knowledge on chemical mechanisms leading to cancer and the tumor progression characteristics which are brought about by molecular changes. With the aid of the developed technologies which can examine the changed cancer cell pathways, it is now easier to trace cancer progression. With the expansion of cancer studies to incorporate the study of Stem Cells (SCs), most research revolves around these cells. SCs are widely known by their ability to renew themselves as they carry out their roles of tissue renovation and replacement (Trosko, Chang and Madhukar, 2000, p265). This ability of these cells can functionally be demonstrated by the study of hematopoietic stem cells (HSCs) through their long term repopulation. Through this process of renewal, the cells can expand and differentiate resulting in varied hierarchical new generations of cells (Wilson, et al, 2000, p.264). In order to undergo through the process of differentiation successfully and keep a pool of stem cell simultaneously, the cells undergo a cell division process which can be described as asymmetrical or symmetrical. Asymmetrical cell division gives rise to a stem cell which is directed to the pool and progenitor cell which is meant for differentiation. On the other hand, symmetrical cell division aims to maintain the pool as well as replicating the differentiated cells by producing identical cells in either side. The main function of mature stem cells in the bodies of living organisms is to maintain the population of somatic cells in tissues (Sell, 2003, p.19),. The following diagram illustrates how the process of cell division is carried out by stem cells resulting in growth and development of a living organism. Diagram illustrating the SCs divisional activities SC development takes place within niches (specific microenvironments) which consist of varied cell types and products. Sell (2003, p.16) asserts that this external environment act as basis of regulating the behavior of stem cells through: expression of genes, molecular regulations, epigenetic regulation. Furthermore, SC production and differentiation balance has to be perfect in order to avoid abnormal tissue growth or tissue loss. Many researchers have tried to come out with explanations as to how the normal functioning of SCs is impaired leading into transformation conditions. Some say that since these cells have the potential to divide extensively giving rise to both SCs and specialized differentiated cells, this may present a possibility of cancer cell development (Trosko, Chang and Madhukar, 2000, p.268). However, others argue that undesirable conditions in the niches cause the SCs to mutate inhibiting their normal processes of self-renewal. Experimental Explanations In cancer, target cells for mutation and alteration is not exactly known, but since SCs are the basis of genetic activities in a living organism, doctors have proposed that SCs might play a key role in carcinogenesis (Sell, 2003, p.25). They argue that the genetic activities of the SCs activate malignant modifications through progenitors of the differentiated cells. A mouse experiment was carried out to how myeloid leukemia results from restricted progenitors. The experiment was designed by manifestation of transgenes particularly limited to myeloid progenitors through the use of hMRP-8 promoter. This mouse model portrays many similarities the human leukemia disease since the imposed anti-apoptotic gene bcl-2 expression in myeloid linage causes disease similar to myelomonocytic leukemia in humans (Wilson, et al, 2000, p.254). Just as earlier said, in cases of leukemia that arise spontaneously in humans, it is possible that SCs cause mutation accumulation that result in neoplastic proliferation. To further investigate whether extra mutations were necessary in synergize of bcl-2 in order to encourage AML, hMRP8-bcl-2, investigators bred the transgenic mice with other mice of 1pr/1pr Fas-deficient (Chang, et al, 2001, p.203). The results indicated that the apoptosis pathway loss caused the development of AML in the mice by 15%. It was observed that the mice’s haematopoietic tissues experienced a myeloblast expansion and this was accompanied by a decrease in granulocytes number. In trying to explain why only 15% of AML-bcl-2 expression was inherited in the progressive generation, it was said that perhaps progenitors in the mice acquired new mutations that prevented the process of self-renewal in some cells (Trosko, Chang and Madhukar, 2000, p.271). It was concluded that if a single extra mutation can have such intense transformations in the cell function, then a gain-of-function mutations may transform normal functioning cells to cancer through proliferation. The Cancer Stem Cell (CSC) Theory The Cancer Stem Cell (CSC) theory is based on the premise that tumors are composed of a cellular hierarchy which is like a sketch of the tissue which was transformed (Trosko, 2004, p.232). Two main observations lead to this basis: first because tumors generate from one cell, however not all tumor cells are identical leading to what is termed as tumor heterogeneity. The tumor heterogeneity characteristic comes about due to the instability of the microenvironment within the tumor forcing tumor cells to transform in their quest for adaptability. The second observation was based on the view that many cancer cells were necessary for a tumor to grow. Unfortunately, most cancer cells have been found to lack the proliferation capability but instead transform due to environmental differences (Sell, 2003, p.22). Hence SCs must play a very big role in both the formation of cancer cells as well tumor growth. According to this theory, only few tumor cells and cancer cells can cause tumorigenic (Wilson, et al, 2000, p.246). These cells can only divide to give rise to both self-renewing cells and non-self-renewing cells, explaining further the existence of heterogeneous cells in a tumor. By so saying, it implies that CSCs initiate the process of tumor growth and development. These pre-existing growth hierarchies are used by the cancer cells to further heterogeneity in tumors. There is evidence that indicates that cancer cells are not tumorigenic as a whole but rather only a fraction of them has the ability to self-renewal facilitating tumor development. The most considered experiment explaining this is that of Brunschwig and Southam of 1966. Chang, et al, (2001, p.202) suggests that by this time claims were being made that malignant cells can be found in the blood of patients with cancer but only few of them could cause tumorigenic. Through the experiment it was affirmed that a large number of CSCs is needed to grow a tumor. Summary Despite of all these new discoveries, knowledge and advances relating to cancer, cancer remains a threat to life worldwide. Trosko, (2003, p.44) contends that the reason behind this is the fact that most people do not understand its manifestations in the early stages and only seek help when it is too late. In addition, the ability of cancer to recur after early therapies presents a great challenge to people suffering from the disease. Recurrence may result partly due to the presence of CSCs within the body of the treated patients. As a result, CSCs can be considered to be the source of cancer and the subsequent recurrence. Fortunately, researchers are coming up with new and better therapeutic approaches to curb this problem. These new approaches aim at the malignant cells in order to stop their heterogeneous divisions. However, this has not been easy since some CSCs exist as chemoresistant phenotypes making it difficult to be made cancer drugs sensitive (Wilson, et al, 2000, p.251). Above all every individual is advised to carry out regular check-ups to ascertain his/her cancer status. Most importantly, prevention has been emphasized and one of the ways one can do this is through exercise. References Ballard-Barbash, R., et al, 2006, Obesity and body composition, In: Schottenfeld, D., Fraumeni, F., editors, Cancer Epidemiology and Prevention, 3rd ed, New York: Oxford University Press.  Chang, C., et al, 2001, A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis. Radiat Res; 155(2): 201–207. Giovannucci, L., 2005, A prospective study of physical activity and incident and fatal prostate cancer, Archives of Internal Medicine, 165(9):1005–1010.  Holmes, D., et al, 2005, Physical activity and survival after breast cancer diagnosis. Journal of the American Medical Association, 293(20):2479–2486.  Lee, I. and Oguma, Y., 2004, Physical activity, In: Schottenfeld, D., Fraumeni, F., editors, Cancer Epidemiology and Prevention, 3rd ed, New York: Oxford University Press.  McTiernan, A., editor, 2006, Cancer Prevention and Management Through Exercise and Weight Control, Boca Raton: Taylor & Francis Group, LLC.  Reya, T., et al, 2001, Stem cells, cancer, and cancer stem cells, Nature; 414: 105–111. Sell, S., 2003, Cellular origin of cancer: dedifferentiation or stem cell maturation arrest? Environ Health Perspective; 101(5): 15–26. Tardon, A., et al, 2005, Leisure-time physical activity and lung cancer: A meta-analysis, Cancer Causes and Control , 16(4):389–397.  Trosko, E., 2003, The role of stem cells and gap junctional intercellular communication in carcinogenesis, J Biochem Mol Biol; 1: 43–8. Trosko, E., 2004, Radiation-induced carcinogenesis: paradigm consideration. In: Calabrese, J., editor. Biological effects of low level exposures. Boca Raton, FL: CRC Press: 205– 41. Trosko, E., Chang, C., and Madhukar, V., 2000. Cell-to-cell communication: relationship of stem cells to the carcinogenic process, Prog Clin Biol Res; 331: 259–276. Wilson, R., et al, 2000, Gap junctions and the regulation of cellular function of stem cells during development and differentiation, Methods; 20: 245–64. Read More