Research Proposal: The role of perivascular macrophages in breast cancer metastasis. 1. Specific Aims
The tumour microenvironment is comprised of both malignant and non-malignant cells. Increasing evidence suggests that the fate of malignant cells is altered by the behaviour of the surrounding nonmalignant cells. Together, the diverse composition of the microenvironment, including immune cell infiltration, stromal cells and extracellular matrix, as well as nutrient and oxygen supply, shape the fate of cancerous cells. In particular immune cells impact on tumour growth and metastasis.
The co-evolution of tumour cells along with the immune system results in a continually changing and immune-suppressive or -permissive environment (1). Therefore, understanding anti-tumour immune responses carries high potential for therapy. Indeed, the last years have seen a revolution in the use and success of anti-cancer immune-therapies. Nevertheless, cancers inevitably escape the immune system. Under certain conditions, malignant cells may even exploit immune cells for their spread, especially the tumour macrophage population (2, 3). Thus, there is the great need to better understand how immune cell subsets contribute to cancer progression.
Clinical studies suggest that in almost 80% of the solid tumours, the presence of elevated macrophage numbers is associated with disease progression and poor prognosis. The tumour microenvironment has been shown to educate the macrophages to perform roles that are supportive of tumour development and metastasis instead of the pre-programmed anti-tumoural functions. Our understanding of macrophages in the tumour microenvironment has till date been restricted due to the heterogeneity in the macrophage population ...
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... role of PVM by their selective depletion in vivo will provide the ultimate validation of their role during breast cancer development and metastasis. 4. OUTCOMES AND SIGNIFICANCE
Invasion of distant organs by tumour cells requires their dissemination through blood vessels and/or lymphatics. Thus, it is imperative to understand the precise pathways that guide tumour cell intravasation. In this application, we will determine the role of a thus-far understudied player in this process, namely PVM. The availability of a transgenic mouse strain that facilitates the identification of PVM in combination with cutting edge imaging technology puts us in an ideal position to obtain novel information on this innate immune cell subset. In addition, we believe that our experiments will increase the knowledge of the contributions of macrophages to the regulation of tumourimmunology.
If lymphatic cancer is found treatment is required immediately to get rid of the cancer cells as soon as possible so damage as is not done to normal cells.
The acquisition of an immortalized proliferative potential is very important for human tumors because, otherwise, the tumors will not grow in number nor will they metastasize. Mutations in progenitor cells would not be transmitted too far as they have limited replication and proliferation ability. Thus, the growth of the tumors will be limited. Hence, if there is even a very small population of cells with the ability to proliferate continuously, there will be a source for productions of more cells for the tumor. Clonogenic assays have shown that, though most cells in a tumor have a limited ability to proliferate, a subset of cancer cells exist in these tumors that continuously proliferate and give rise to new tumors on transplantation.
“Cells Involved In Immune Responses and Antigen Recognition.” Microbiology and Immunology. Web. 18 Dec. 2011. .
..., while a cell undergoes cell cycle, when a cell comes in contact with another cell, it stops reproducing. However, cancer cells continue to duplicate repeatedly until there is a mass of cells or a tumor to form (see figure 9). Lastly, in cell division when there is a mutation or abnormality in the DNA, a normal cell stops dividing. However, a cancerous cell will continue to duplicate and form mutations (“Cell Biology and Cancer”). Also, cancer cells are harmful because they grow and duplicate with complete disregard to the functions and limitations of the body (see figure 10). Also, cancerous cells have the ability to spread through metastasis throughout parts of the body through the bloodstream. In terms of similar behavior to that of normal cells, cancerous cells also duplicate, but at a very different rate ("Cancer Cells vs. Normal Cells: What's Different?").
Over the past decade breast cancer has become one of the most predominant diseases in the United States. Breast cancer starts out as a malignant tumor in the tissues of the breast which is formed from the uncontrolled growth of abnormal breast cells. Breast cancer is the most common cancer in women, but it can also appear in men. (Stephan, 2010)
Breast cancer is most commonly diagnosed in Stage I and Stage II, where the size of the tumor is less than five centimeters in diameter. In these situations, surgery is often the second treatment option after chemotherapy and radiation therapy, both of which are used to shrink the tumor to a manageable size first. If the patient chooses to, the ...
The direction of osmosis depends on the relative concentration of the solutes on the two sides. In osmosis, water can travel in three different ways. If the molecules outside the cell are lower than the concentration in the cytosol, the solution is said to be hypotonic to the cytosol, in this process, water diffuses into the cell until equilibrium is established. If the molecules outside the cell are higher than the concentration in the cytosol, the solution is said to be hypertonic to the cytosol, in this process, water diffuses out of the cell until equilibrium exists. If the molecules outside and inside the cell are equal, the solution is said to be isotonic to the cytosol, in this process, water diffuses into and out of the cell at equal rates, causing no net movement of water. In osmosis the cell is selectively permeable, meaning that it only allows certain substances to be transferred into and out of the cell. In osmosis, the proteins only on the surface are called peripheral proteins, which form carbohydrate chains whose purpose is used like antennae for communication. Embedded in the peripheral proteins are integral
According to “Medical News Today” cancer is a disease that is caused by an over growth of anomalous cells on one or more lungs. Cells often go up the air pipes which can cause difficulty to breath. Due to the over production of cells the tissue cells often begin to over produce; which results in tumors. There are two types of tumors: malignant and benign. Malignant tumors are the more dangerous of the two due to its invasive nature; which makes it cancerous. While benign is not invasive in other words non-cancerous. This is why cancer spreads to multiple areas and can be sometimes very difficult to fight. Cancer cells are abnormal not only because of their evasive nature, but also because of its irregular life cycle. Rather than expire like a regular cell, they continuously grow and duplicate which causes the disease to spread. This makes cell abnormal in shape and other qualities; known as a sickle cell. Due to the large growth and reproduction rate of the cells this makes the spreading of the cancer more rapid. Each cancer has specific symptom, for lung cancer the sympto...
Cancer cells have spread to lymph nodes near or far from the prostate, or to other organs and tissues, such as the liver or lungs.
Tumors are formed by the alteration of the body’s own cells. This can be caused by environmental factors such as radiation, like UV exposure, chemicals or viruses 1. These can disrupt genes that control growth and cause an increase in cell division and proliferation. Proto-oncogenes are those genes that control normal but essential cell processes that keep cell growth and death in check. Two important categories are apoptosis genes, which regulate cell death, and tumor suppressor genes, which decrease cell propagation 1 . If these genes were mutated to the point where they cannot produce a functioning protein, cell division would continue far past what it was supposed to and unhealthy cells would be allowed to live and continue to multiply. This is what creates a malignant tumor. Certain conditions in the body can also promote the growth of cancer cells. One of these is a deficiency of natural killer (NK) cells, which are able to kill cancer cells by creating a pore in the cell membrane with perforin and releasing granzymes into the cell. Low levels of perforin allow for tumor growth 1. Chronic inflammation can also ...
Here, deep in the lungs, oxygen diffuses through the alveoli walls and into the blood in the capillaries and gaseous waste products in the blood—mainly carbon dioxide—diffuse through the capillary walls and into the alveoli. But if something prevents the oxygen from reaching t...
Healthy cells grow and divide in a way to keep your body functioning properly. But when a cell is damaged and becomes cancerous, cells continue to divide, even when new cells aren't...
Breast Cancer is defined as “a group of solid tumor malignancies arising in the tissues of the breast” (Sarah Crawford, Richard Alder, 2013) in human and other mammals. It can happen to both men and women. For women, breast cancer is one of the leading causes of cancer death. According to National Cancer Institute, in the United States, the 2014 estimated new cases and deaths of female from breast cancer are 232,670 and 40,000, respectively. For male, it’s 430 deaths out of 2,360 new cases. From these numbers, we can see that women in the U.S. are greatly affected by breast cancer, thus, it’s not difficult to imagine the impact on a worldwide level. Although these numbers look frightening, people can actually survive from breast cancer if it is detected early and treated properly, so it is extremely important for all of us, especially women, to have a better understanding of breast cancer.
Adaptive immune system happens much quicker to the presence of an “infection creating potent mechanisms for neutralizing or eliminating the microbes. There are two types of adaptive immune responses: humeral immunity, mediated by antibodies produced by B lymphocytes, and cell-mediated immunity, mediated by T lymphocytes.”
This report provides an insight into the differences in the structure of cells and the way that they carry out their internal mechanisms. Cells form the basis of all living things and they are the smallest single unit of life. Cell biology is the study of cells and how they function, from the subcellular processes which keep them functioning, to the