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Metastatic cancer is a cancer that has spread from the part of the body where it started (the primary site) to other parts of the body. When cancer cells break away from a tumor, they can travel to other parts of the body through the bloodstream or the lymph system. (Lymph vessels are much like blood vessels, except they carry a clear fluid and immune system cells.)
Metastasis depends on the cancer cells acquiring two separate abilities -- increased motility and invasiveness. Cells that metastasize are basically of the same kind as those in the original tumor. If a cancer arises in the lung and metastasizes to the liver, the cancer cells in the liver are lung cancer cells. However, the cells have acquired increased motility and the ability to invade another organ.
The spread of a malignancy into body cavities can occur via penetrating the surface of the peritoneal, pleural, pericardial, or subarachnoid spaces. For example, ovarian tumors can spread transperitoneally to the surface of the liver.
As an alternative or complimentary hypothesis to the view that normal macrophages facilitate the metastatic spread of neoplastic stem cells; the myeloid hypothesis of metastasis suggests that metastatic cancer cells arise directly from cells of myeloid origin or from hybrid cells following fusion between macrophages and non-metastatic stem cells.14,28,39,55 The myeloid cell origin of metastasis would also encompass the macrophage fusion hypothesis of metastatic cancer, since it is the properties of macrophages that contribute to the metastatic cascade.60,61 Myeloid cells are already mesenchymal cells and would not, therefore, require the complicated genetic mechanisms proposed for the EMT in order to metastasize. Macrophages arise from the myeloid lineage and have long been considered the origin of human metastatic cancer.17,28,60,62-64 Macrophages can fuse with epithelial cells within the inflamed microenvironment thus manifesting properties of both the epithelial cell and the macrophage in the fusion hybrids.31,65,66 The origin of metastatic cancer from hematopoietic stem cells or yolk sac-derived macrophages is also consistent with the myeloid cell hypothesis.67 The uncontrolled growth of these cells can arise following respiratory damage in their homotypic fusion hybrids. In his recent review on metastasis, David Tarin states: “..it would appear that tumour metastasis first appears in the lower chordates in parallel with the origin of lymphocytes and this may indicate that metastasis cannot occur until an organism has evolved the genes for lymphocyte trafficking.”1 According to our hypothesis, it is hematopoietic stem cells themselves or their lineage descendants that become the metastatic cells either through direct transformation in the inflamed microenvironment or through their fusion with neoplastic tumor cells.
Metastasis is a multi-event complex process that involves the ability of tumor cells escaping the primary tumor to colonize a novel microenvironment. The fact that cancer patients might develop metastasis years or even decades after diagnosis makes understanding the metastatic process very difficult. New technologies have allowed new insights into the genetics and genomics of metastasis. Here, we discuss advances in the current understanding of the principles of metastasis, and a number of the emerging technologies that might lead to benefits in the clinical realm that will alleviate the morbidity and mortality associated with metastasis.Keywordsbreast cancer, gene expression, genetic background, genomics, invasion, metastasis, microarray, mouse models, polymorphism, progression, tumor
About this course: Over 500,000 people in the United States and over 8 million people worldwide are dying from cancer every year. As people live longer, the incidence of cancer is rising worldwide, and the disease is expected to strike over 20 million people annually by 2030. Everyone has been, or will be touched by cancer in some way during their lifetime. Thanks to years of dedication and commitment to research we’ve made enormous advances in the prevention and treatment of cancer, But there is still a lot of work to be done. In this course, physicians and scientists at the Johns Hopkins School of Medicine explain how cancer spreads or metastasizes. We’ll describe the major theories of metastasis and then describe the biology behind the steps in metastasis. The course also describes the major organs targeted by metastasis and describes how metastases harm the patient.
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