Metastatic Cancer: Types and Causes

Metastatic crabmeat Types and Ca habitsIntroductionCancer is something that m some(prenominal) people face or is affected by in some way. Cancer is a problem that is global and al shipway ontogeny affecting more(prenominal) people as the worlds people increases. The 2012 statistics show that were about 3.45 million new cases of pubic louse and 1.75 million deaths as a resultant portion of crabby person worldwide in the year 2012. The chief(prenominal) tidy sumcer put world summit contributing 464,000 cases Ferlay, Foucher, Tieulent, Et.al, 2013. Thanks to a better checking and better treatment of genus Cancer deal chemotherapy and keistercer based drugs, there has been a decrease in death from erectcer and so better survival rates for both males and females affect by substructurecer Jemal, Simard, Dorell, Et.al, 2012. The fact malignant neoplastic disease is so prevalent worldwide is cod to the umteen features and ways that cancer affects people. One of these fe atures is that some cancer mobile phones argon not static. The cancer carrels argon up to(p) to alter and change in order to form into another cancer that is in another rive of the system therefore affecting a different organ site. This index for cancer carrelphones to move or migrate to different separate of the corpse is know as Metastasis Yachida, Jones, Bozic, Et.al, 2010 Fokas, Cabillic, Et.al, 2007. The fact that cancer booths are able to migrate to other sites of the ashes is not just random. Where the cells migrate to, is dependent on where the cancer cells was originally was before the migration. What dictates where the cancer cells go, are specific stimuli or environment deep down the body so that the cells are able to climb up into tumors. The stimuli or environment may consist of specific receptors or chemokines that are shared or common amid the two sites Baruch, 2009. When cancer has metastasised to a different area the site that the cancer had orig inated in is known as the primary(a) cancer and the site at which the cancer cells moved to is known as metastatic cancer. A common final result of metastasis is from breast to hotshot, with breast being the primary cancer and brainpoweriac being the metastatic cancer. depreciator cancer is often found to metastase to the brain, the chances of this occurring are increased when patients have HER2 oer port Gupta, Adkins, Et.al, 2013. HER2 comes from the human epidermal harvest-festival factor receptor family that fancys retort such as cell evolution and cell differentiation, therefore it can be easily predicted that over side of HER2 leads to un moderatelable cell growth a feature that is in all cancers Rubin Yarden, 2001. The metastasises of cancer within patients does not affect them straight away, as it often takes years for the metastatic cancer to be detected and to affect the person. When the primary tumor has grown, only indeed will the tumour cells migrate and invade to another part of the body and grow at the site. When the tumour cells are at the new site then they the turn of cell growth occurs at the site. But it has been shown that the tumour cells at the new site have been dormant which accounts for the time surrounded by the detection of the primary cancer and the metastatic cancer Rcken, 2010. The way the metastatic cancer cells move from their primary site to their metastatic site can be many ways depending on ultimately were the tumour organization will be formed in. Examples of the fecal matter or migration are 1) local anesthetic tissue invasion which is movement of the tumour cells through the tissue, 2) hematogenous spread which is the movement through the blood 3) lymphatic spread which similar to the blood by uses the lymph nodes and finally 4) spreading through surfaces and cavities Pepper, 2001. in that respect are many sites of metastatasis, below is a succinct tabularise of the sites and where they originated f rom Nguyen, Bos, Massagu, 2009.Table 1 A legal brief summary list that shows the sites of metastasis from primary tumours Nguyen, Bos, Massagu, 2009.A metastatic cancer that is peculiarly important and of interest is metastatic cancer that is able to migrate to the brain. From the table above it can be seen that sites of metastasis for the brain is only in 3 types of tumours, these being breast, lung adenocarcinoma and skin melanoma. Out of these three types lung and breast tumours unremarkably metastases to the brain making up 60% of brain metastasises Nguyen, DeAngelis, 2004. The occasion wherefore brain metastasis is of particular interest is be build of how the metastatic cancer is able to depict through the blood brain roadblock (BBB). In order to understand the movement of the blood brain barrier it structure must archetypical be looked at. The blood brain barrier is made up of 4 main sections or parts that are of important to it voice. These 4 parts are 1) ridiculous junctions, 2) adherens junctions, 3) astrocytes, and 4) pericytes, each section has its own run for as well. The tight junctions are made up of claudin, occludin, and junction adhesion molecules these are transmembrane proteins which are involved in cell-to-cell adhesion. Adheren junctions are responsible for paracellular permeability. Astrocytes are for geomorphological supports and as well as for guiding of neurons and finally the pericytes are for mechanical support for cell attachment. Lawther, Kumar, Krovvidi, 2011 Hawkins, OKane, Simpson, Et.al 2006.Figure 1 Image showing the main parts of the BBB and the overall structure of the BBB. Image was extracted from Lawther, Kumar, Krovvidi, 2011.Now that the structure of the blood brain barrier can be seen more clearly, a better understanding of how metastatic brain tumours form and how the cells pass through the blood brain barrier. more specifically primary breast cancer that produces metastatic brain tumour can be looked at. The tumour cells that are being metastasised are able to express vascular endothelial growth factor (VGEF). The manifestation of the vascular endothelial growth factor by the tumour cells is able to take apart the blood brain barriers permeability which allows the cells to pass through and into the brain Gerstner, Fine, 2007. another(prenominal) way to metastasise to the brain is by the tumour breast cells attaching or invading the brain microvascular endothelial cells and then passes through the blood brain barrier Arshad, Wang, Sy. Et.al, 2011. The survival rates of patients that have a metastatic brain tumour in unfortunately not very high. Those patients that have had primary breast cancer and then later gained a metastatic brain tumour have between 30-40% chance of death due to the metastatic brain tumour Wadasadawala, Gupta, Bagul, 2007 Jaboin, Ferraro, DeWees, Et.al, 2013. There are treatments available that help mesh against metastatic brain tumours the main one and mos t effective being radiotherapy. However the effectiveness of radiotherapy is dependent of where the tumour cells had originated from i.e. which primary cancer the patient had first. Those that had primary lung or breast cancer are more sensitive to the radiotherapy treatment. Other types of treatments intromit Craniotomy, Postoperative radiotherapy, and Stereotactic radiosurgery. The treatment that is craniotomy is not used often as it is stressful for the patients. Postoperative radiotherapy is also an effective treatment that improves the life of the person, however there are situation effects or conditions that can occur as well equivalent disorder of the nervous system or dementia. The final treatment declared is Stereotactic radiosurgery which involves using gamma radiation on the site of the tumour Shibui, 1999. With the use of radiation is the fear of persevering the nearby cells and tissues. With the advancement of science and engine room the treatment of using radiother apy has become better. The use of radiotherapy is button up the main treatment but with better radiotherapy offsetes and technique the delivery of the cells and tissue from radiation has greatly improved Owonikoko, Arbiser, Zelnak, Et.al, 2014.epithelialmesenchymal alteration (EMT)Epithelialmesenchymal transition (EMT) is defined as a biological process that occurs within polarised epithelial cells which interact with the basement membrane. The polarised epithelial cells undergo many biological changes that brings about a mesenchymal cell phenotype, these changes include an increased ability of migration, invasion and develop a resistance to the process of apoptosis Kalluri Weinberg, 2009. There are keys differences between the epithelial cells and the mesenchymal cells. Epithelial cells are cells that form layers, which are tightly packed by membrane structure such as tight junctions, gap junctions adherens junctions and desosomes. These cells do possess an ability of motility , however under habitual condition they remain they do not move. In comparison the mesenchymal cells are not organised into layers like epithelial cells. The main difference between the two is that mesenchymal cells are very motile whereas epithelial are not commonly Thiery Sleeman, 2006.The whole process of epithelialmesenchymal transition plays a affair in normal development. These normal developments include gastrulation which is an early phase in embryonic development and heart morpho agentsis which need and take advantage of the transition between the epithelial cells into mesenchymal cells. Another key role of the EMT is that it is for the down linguistic rule of E-cadherin Larue Bellacosa, 2005. E-cadherin is a tumour suppressor that is encoded by the Cadherin-1 (CDH1) ingredient that is key for the downsizing of carcinoma progression. It has been found and seen that the loss of the Cadherin-1 at EMT sites are linked to the formation, development of cancer. The reason for this is due to the fact that the loss of the E-cadherin increases the ability of invasion in cells Wang Shang, 2013.As with any biological process there are arrangement factors that fetch and regulate the transition. The transcription factors that mediate the processes are SNAI1 which down regulates E-cadherin, Zinc riff E-box (ZEB) and also basic helixloophelix transcription factors Lamouille, Xu, Derynck, 2014. There are features and properties of the mesenchymal cells that can be linked to cancer if not adjust properly. The mesenchymal cells are able to produce and secrete chemokines and growth factors that stimulate cell growth and angio componentsis. Another key feature of the mesenchymal cells is that they have anti apoptotic properties that can stop or save cells from undergoing apoptosis Murphy, Moncivais, Caplan, 2013. Just from seeing the features of the mesenchymal cells it can easily be seen that if the regulation of the process, variance or changes in lookin g at occur the consequences can be predicted and linked to the formation of cancer. The final manifestation of epithelialmesenchymal transition is how it is linked to the formation of cancer and more specifically metastatic cancers. As stated epithelialmesenchymal transition is regulated by many growth factors and proteins such as Epidermal growth factor, Hepatocyte growth factor and Transforming growth factor beta, all of which if changed by mutation or expression can ultimately contribute to the hallmarks of metastatic cancer like uncontrollable cell growth and invasion into other tissues and organs in the body which is the main feature of metastatic cancer Gos, Mioszewska, Przybyszewska, 2009. on a lower floor is a diagram that summarises and shows the process of how epithelialmesenchymal transition can labor the formation of metastatic cancer Kongemail, Liemail, Wangemail, Et.al, 2011.Figure 2 A summary of how epithelialmesenchymal transition can be linked to metastatic cancer . EMT is the process of epithelialmesenchymal transition and MET is the process of MesenchymalEpithelial Transition. Image taken from Kongemail, Liemail, Wangemail, Et.al, 2011.The moving picture above shows the transition of a primary tumour into a metastatic tumour and reason for this to happen. Red arrows show aspects that may be departed wrong due mutation or change in expression through methylation.EpigeneticsEpigenetics is the genetic control by using factors that does not include a persons deoxyribonucleic acid sequence Simmons, 2008. Epigenetic control or regulation is the process whereby genes are activated or deactivated within a cell Mitsuyoshi Nakao, 2001. Essentially the concept of epigenetics is the change in gene expression that can be caused by certain mechanisms such as desoxyribonucleic acid Methylation or Histone modification. These changes in gene expression whereby expression of a gene is switched on or off can be inherited and passed on. The mood of epigene tics and its mechanism is needed for maintenance of genes that are specific to tissues. Changes in the process of epigenetics, like desoxyribonucleic acid Methylation or Histone modification causes disruptions in a genes function, which alters its expression and is one of the hallmarks of how cancer begins Sharma, Kelly, Jones, 2010. As stated there two ways that can causes changes, histone modification and DNA methylation which will be the main contract of this paper. The process of histone modification to a certan extent is reversible depending on the type of modification. The process of DNA methylation is more long term creating long-term repression Cedar Bergman, 2009. DNA methylation is the common mechanism in which genes are activated or deactivated by the addition of a methyl group to cytosine or axerophthol bases, making it an epigenetic signal tool. Changes in the process of DNA methylation can result in a gene being constantly activated or deactivated which can lead to brain tumours or other tumours in the body Phillips, 2008. The process of DNA methylation is catalysed by the family of enzymes known as DNA methyltransferases. DNA methyltransferases is an important enzyme in epigenetic silencing of transcription. As this is a family of enzyme there are many types of DNA methyltransferases which are DNMT 1, DNMT 2, and DNMT 3 each one having their own function Simmons, 2008 Fakhr, Hagh, 2013. There are two types of DNA methylation these are 1) Hypermethylation and 2) Hypomethylation. Hypermethylation stops transcription in the champion expanse of suppressor genes which ultimately lead to gene silencing Das Singal, 2004. The location at which hypermethylation occurs at are known as CpG sites, these are sites were cytosine is next to guanine. It is the cytosine in these CpG sites that are usually methylated and therefore switched off Esteller, 2002. Hypomethylation is the loss of methylation at partings or sites that are normally heavily methylat ed, for example satellites like sit 2. The loss of the methylation at SAT 2 can lead to instability and oncogene activation (Jin, Li Robertson, 2011). Oncogenes when activated increases protein expression which in turn leads to increase in cell division, decreases in cell differentiation and the inhibition of cell death Chial, 2008. It is the mutation of a proto-oncogene by hypomethylation that makes an oncogene which is the cause of increase in cell division and therefore the cause of an abnormal growth of cells that leads to tumours and cancer. A proto-oncogene is the normal, non-mutated gene that regulates cell division making it controllable by balancing cell growth and death. There many types of proto-oncogenes these include WNT, RAS and ERK Chial, 2008 Torry, Cooper, 1991. To summarise the image of Epigenetics is the control of gene expression using DNA methylation or Histone modification. If any of these two processes are damaged or mutated this then means the control of ge ne expression can no long be controlled and so this leads to increase in cell growth and therefore tumours and cancer.Methylation of Promoter domainThe DNA methylation of the operator region within genes is as stated an epigenetic event that is linked to transcriptional silencing in cancer. This means that DNA methylation in this region is for the control of gene expression Yang Park, 2012. The promoter region of gene is a region that starts or causes the initiation of transcription Gordon, Chervonenkis, Gammerman, 2003. The process of methylation in the promoter region causes the expression of genes to reduce or in the in case of cancers cause the silencing of the gene altogether. There are two ways that this happens in the promoter region. One of the ways it can occur is the inhibition of sequence-specific transcription factors which post CpG sites. The second way is by the use of methyl-CpG binding proteins which can fight for binding sites of methylated DNA Robertson Jones , 2000. E-cadherin was introduced to have a key role in epithelialmesenchymal transition. If there is methylation more specifically hypermethylation in the promoter region of the E-cadherin then this can cause the silencing of the gene which has been linked to many types of gastric cancer also known as stomach cancer Tamura, Yin, Wang, 2000. Another gene that is important and methylation of it has been shown and linked to astrocytic brain tumour is the Methylguanine-DNA methyltransferase (MGMT). Methylguanine-DNA methyltransferases function is as a repair protein that can get hold of promutagenic alkyl groups guanine in DNA. DNA methylation in the CpG Island of the Methylguanine-DNA methyltransferase means that its function in order to remove promutagenic alkyl groups is decreased Nakamura, Watanabe, Yonekawa, Et.al, 2001.