The role of Perivascular Macrophages in Breast Cancer Metastasis.
1. SPECIFIC AIMS
The solid tumor microenvironment is comprised of both malignant and non-malignant cells and an increasing body of evidence suggests that the fate of malignant cells can potentially be altered by the behavior of the surrounding non-malignant cells. It is becoming increasingly evident that the modulation of tumor microenvironment has an important role to play in tumors displaying their full neoplastic potential and thus targeting the surrounding non-malignant cells particularly the immune cells as potential therapeutic targets is not unheard of. In the last decade the general concept for tumour development has seen a large shift in relation to immune cells. Novel functions implicating immune cells as protumoral have come to the forefront. The immune subset that is usually implicated in this behavior is the tumor macrophage population. Clinical studies suggest that in almost 80% of the solid tumors, the presence of elevated macrophage numbers is associated with disease progression and poor prognosis. The tumor microenvironment has been shown to educate the infiltrating monocytes to perform roles that are supportive of tumor development and metastasis. But the macrophage population within a tumor microenvironment is quite heterogenous and not much is known about the role of various macrophage subsets in tumor cell dissemination and metastasis. Our laboratory has generated a transgenic mouse strain that allows for the identification of a unique subpopulation of tissue resident macrophages localising in the perivascular space along the post-capillary venules and lymphatics (hereafter referred to as perivascular macrophages; PVM) (Fig. 1). We have sho...
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...amely 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 m to the regulation of tumour-immunology
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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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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. .
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.... Glioma-initiating cells: a predominant role in microglia/macrophages tropism to glioma. Journal of neuroimmunology 232, 75-82.
About 12% of women in the United States will develop breast cancer in their lifetime, more than any other type of cancer (www.breastcancer.org, 2015). Many people lack the knowledge of how breast cancer is developed. Some people think they will not get cancer because they do not smoke cigarettes, but this is not the only cause of cancer developing in the breast. Anyone can get cancer. Everyone is potentially at risk for developing some form of Cancer (American Cancer Society, 2015).
Our immune system protects our bodies from pathogens like bacteria and viruses very efficiently in most cases. One big question that has come up is why does the immune system not respond to cancerous cells in the same way? Why are cancer cells not eradicated like other dangerous foreign cells? This seems very strange, especially since the immune system has cells that are specific to destroying cancer cells and virus-infected cells, called natural killer cells. To begin to answer this question it is useful to examine cancer cells and their interactions with the immune system in more detail.
There are many different approaches for management of breast cancer and treatment options that patients may select in collaboration with health care providers. Breast cancer is a complex disease that presents in many different types, with specific biological features unique to each patient. Invasive cancers are classified based on tumor type and histological grade, which is of utmost importance when deciding the course of treatment. Contemporary advances in breast cancer treatments have been made, especially in chemotherapy, hormone and biological therapies. Treatment can be a combination of local treatments, systemic treatments, and in some cases, new targeted treatments (Watts, 2013).
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...
Inflammatory breast cancer accounts for 1% to 3% of breast cancers. The skin of the breast looks red and feels warm with no lump: due to cancer cells blocking...
National Cancer Institute. 2 December 2013. April 2014. WHO. World Health Organization.
Dec. 2013. http://www.disabled-world.com/artman/publish/genetic-engineering.shtml Park, Tristen S., Steven A. Rosenberg, and Richard A. Morgan. "Treating Cancer with Genetically Engineered T Cells." National Center for Biotechnology Information. PubMed Central (PMC), 12 June 2011.
Innate system critical main defense is the cellular component; there are several kinds of cells involved in the process. One of the crucial cells is the macrophage. ...
Blood and urine based biomarkers used in molecular pathology are only indicative of the average response of the cell population affected with little or no information of the range of response or variability form areas of tissue (Naddler and Langley 2001)