2.3.5. Tumour-associated macrophages
Macrophages are inherently plastic cells, and this adaptability can be exploited by the tumor to elicit distinct functions at different stages of tumor progression. Less information is available about the complexity of individual macrophage activities and their associated molecular profiles in cancer. Many subpopulations of TAMs exist within a tumor, which probably change temporally during tumor development and geographically depending upon of their location within the tumor micro-environment. For example, TAMs recruited to hypoxic areas promote tumour angiogenesis, whereas TAMs at the tumor–stroma border play an active part in invasion and angiogenesis.
TAMs produce epidermal growth factor (EGF) that
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Association of cancer cells with TAMs throughout the tumour significantly increases their motility, this gets further amplified when cancer cells are found in close proximity to perivascular TAMs. Moreover, cancer cells were observed to invade blood vessels only where perivascular TAMs were located.
Reduction in macrophage infiltration, lead to concomitant decrease in circulating cancer cells. In addition, the EGF–CSF paracrine loop is also important for intravasation, as blocking either signaling pathway lead to a significant reduction in the number of blood-borne cancer cells. Cancer cells and macrophages also use collagen fibres as tram lines to rapidly travel through the stroma. Many of these fibres are tethered to blood vessels, resulting in cancer cells accumulating at these vessels. The density of these fibres is regulated by macrophages, at least during development. (Joyce & Pollard, 2009), (Hanahan & Weinberg, 2011)
2.3.6. Cancer Cells and Cancer Stem Cells
Recent studies suggest that many tumors are heterogeneous containing a pool of clonal subpopulations of Cancer cells and cancer stem cells (CSCs). These tumors contain regions demarcated by various degrees of differentiation, proliferation, vascularity, inflammation, and/or invasiveness; pointing to the existence of a new dimension of
We studied the correlation between the micro-vascular density and type of cells “benign and malignant”: We noticed the higher vascularity of cases of cystitis, compared to the vascularity of malignant tumors, this could be explained by the higher vascularity of the active cells, edema, inflammatory infiltrate and vascular congestion during the inflammatory process.
N-cadherin is a protein encoded by the CDH2 gene. It interacts with the cellular cytoskeleton, and is often involved in cardiac muscle, as well as certain cancers. Being calcium dependent, it helps to maintain cellular structure and integrity. For example, it plays a role in trans-endothelial migration, which involves cell-cell adhesion [3]. The endothelial layer contains many different fibers, as well as pathways that allow attachment for the cadherin protein. Some cancer cells can eventually pass through the endothelium, causing the cancer to become malignant and spread. Cadherins in this case can be used to identify and track the spread of the cells, and further identify common routes of travel through the human vasculature.
Distant metastases are mostly identified in patients of osteosarcoma with the estimation of about 85% after surgery. Mostly they occur in lungs however it may also metastasizes to soft tissues and other different bone. Osteosarcoma is lethal because of pulmonary metastasis with widespread progression that leads to respiratory failure. Tumor metastasis and invasion are multistep complex process in which tumor cells alter cell–extracellular matrix (ECM) associations at the primary tumor site to invade adjacent tissues and thus translocated through the vascular vessels to other systems to form secondary tumors there. MMPs are family of proteolytic enzyme that plays an essential role in tumor metastasis and invasion by breaking the ECM and basement
Knowledge is a powerful tool. This seems to be a basic quality, many do not have this. In Animal Farm a selected few, being the pigs, who have a vast amount of knowledge and use that to their benefit. Instead of using this quality for the greater good of the farm, the pigs use it as a way to manipulate the other animals for their own personal gain. Through the uneven distribution of labor, the alteration of the seven commandments, and the persuasion of Snowballs mischief, the pigs show that abuse of knowledge leads to the manipulation of the uneducated.
The first difference in malignant and benign tumors is how they invade cell tissue. Malignant tumors in general, have a tendency to penetrate tissues, whereas benign tumors don’t though they can add pressure to organs resulting in organ damage1. A simplified
The Handmaid’s Tale by Margaret Atwood Born in 1939 in Ottawa, Canada, Margaret Atwood was raised in northern Ontario, Quebec, and Toronto. She is a renown poet, novelist, literary critic, and environmental activist. Her books have received critical acclaim in the United States, Europe, and her native Canada, along with numerous literary awards. Atwood’s representations of gender tackle the social constructs defining femininity, representations of women's bodies, the economic and social exploitation of women, as well as women’s relations with each other and with men. Atwood is a firm believer that the feminist label can only be applied to writers who consciously work within the framework of the feminist movement.
George Mackaness coined the concept of macrophage resistance and activation in the beginning of the 20th century. He showed that the “inactivation” of macrophages had a lot to do with the pathogen-host interaction. In other words, substances in their respective microenvironments could influence macrophages to attain a particular phenotype (7). This eventually becomes significant when studying cancer and the microenvironment associated with it. One of the most important milestones in the study of macrophages was the their identification as sources of cytokines.
Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).
This ability of malign cancer to make their way across basement membrane and into blood vessels is what makes cancer so fatal and impossible to be cure by surgery alone. The result of metastasis and invasion in normal tissue by cancer cells are often seen as one of the distinctive features of malignancy (Ruoslahti 1996). Even though the ability of invasion and metastasis are one of the hallmarks for cancer, these abilities are not unique to cancer cells as it can also occur during the early development stage of the embryo, in healthy organisms and in many noncancerous diseases (Mareel & Leroy 2003). It does not matter whenever the organism has developed benign or malign cancer, all cancer cells have the ability to disturb the normal cell cycle and threaten the survival of the organism.
Injury to the endothelial cells will then decrease production of NO and this will enable the accumulation of lipids. As the build-up progress and permeability decreases, macrophages infiltration and release of pro-inflammatory cytokines occur. The damage caused by oxidation causes a compensatory response which increases the endothelial adhesiveness to leukocytes and platelets via cell adhesion molecule upregulation. Circulating monocytes and leukocytes initially bind cell adhesion molecules on the endothelial surface, but chemokines are required for recruitment into the subendothelial space. Once monocytes enter the subendothelial space, they may mature into macrophages leading to formation of foam cells and then eventually to the appearance of “fatty streaks” in the arteries. As lesion severity progresses into a fibroatheroma, macrophages, T-cells and mast cells penetrate the cap edges and stimulate the production and movement of vascular smooth muscle cells. Vascular smooth muscle cells contribute to plaque growth through producing pro-inflammatory cytokines that attract and activate leukocytes, generate VSMC proliferation, express adhesion molecules that
Cancer is defined as unregulated growth of cells that deviate from usual cellular activities (NIH, 2015). This includes the development of tumors and eventually the invasion of other tissues. Metastasis of tumor cell undergoes multiple steps: invasion, intravasation, extravasation, survival and proliferation (Sethi & Kang, 2011; Van Zijl, Krupitza, & Mikulits, 2011). As GJPs have been described to provide a conduit for intracellular communication, it has been shown in many reports where connexin channels provided the means of initial metastatic lesion formation to the vasculature. Once the metastatic tumor cells invade into the blood circulation (intravasation), these cells will then be able to spread to other locations (i.e. from the breast to the brain).
Tumor recruitment and reprogramming (R&R) of bystander cells in cancer progression. We reported that cancer cells could transform normal host cells in xenograft tumor formation (REF). Using 3-dimensional (3-D) cancer-stromal co-culture and chimeric xenograft tumor formation, we identified that, inside a cancer cell population, there existed a subgroup of metastasis-initiating cells (MICs). Importantly, we found that MICs function as “drivers” to recruit and reprogram dormant cells to become an integral part of the tumor (REF). Bystander cell R&R may be one of the strategies for cancer progression and metastasis. CTCs represent the spreading and metastasizing cancer phenotype and thus represent MICs at metastatic sites. Thus, our proposed work will have important implications in cancer biology (REF). The biomarker and biological behaviors we are able to associate to CTCs will provide confident predictors for cancer progression and clinical response.
Hypoxia is a characteristic feature of most solid tumors. Hypoxia induces tumor chemoresistance in proportion to distance from the vasculature. Hypoxic cells are exposed to less chemo
One day, three witches tell Person A that he will be ruler. Once he tells his wife of this good news, she uses society’s expectations to pressure him into killing the current king/good friend of his, Duncan. She tells him that he’s a coward if he doesn’t do it and that it would make her happy. Is it wrong to make your wife happy? Macbeth asks readers this very question. It allows readers to look into motives, moral development, and the results of murder. It also allows them discover that moral motives do not justify immoral actions.
Cancer is one of the most dangerous and fatal diseases, which is caused by uncontrolled growth and proliferation of cells. Cancer cells’ survival, progression and metastasis are tightly associated with the cellular components. For example, when cells metastasizing, they use cell protrusion which provided by actin cytoskeleton to penetrate the extracellular matrix, they also secrete plasminogen activator to increase protease plasmin’s activity in order to penetrate the membrane. Then some of the tumor cells transfer to another tissue and form metastatic tumor. The specific functions of several cell structures and transporters in tumor cells are discussed as follows.