<unk> astatic tumors are very common in the late stages of cancer. The spread of<unk>  may occur via the blood or the lymphatics or through both routes. The most common sites of<unk>  are the lungs, liver, brain, and the bones. Currently, three main theories have been proposed to explain the<unk> astatic pathway of cancer: the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition <unk>  hypothesis (1), the cancer stem cell hypothesis (2), and the macrophage–cancer cell fusion hybrid hypothesis (3). Some new hypotheses were suggested as well, i.e., under the effect of particular biochemical and/or physical stressors, cancer cells can undergo nuclear expulsion with subsequent macrophage engulfment and fusion, with the formation of cancer fusion cells (CFCs). Factors involved<unk>  involves a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, via the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor and attach to and degrade proteins that make up the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues. By degrading these proteins, cancer cells are able to breach the ECM and escape. The location of the<unk>  is not always random, with different types of cancer tending to spread to particular organs and tissues at a rate that is higher than expected by statistical chance alone. Breast cancer, for example, tends to<unk> e to the bones and lungs. This specificity seems to be mediated by soluble signal molecules such as chemokines and transforming growth factor beta. The body resists<unk>  by a variety of mechanisms through the actions of a class of proteins known as<unk>  suppressors, of which about a dozen are known. Human cells exhibit different kinds of motion: collective motility, mesenchymal-type movement, and amoeboid movement. Cancer cells often opportunistically switch between different kinds of motion. Some cancer researchers hope to find treatments that can stop or at least slow down the spread of cancer by somehow blocking some necessary step in one or more kinds of motion. All steps of the<unk> astatic cascade involve a number of physical processes. Cell migration requires the generation of forces, and when cancer cells transmigrate through the vasculature, this requires physical gaps in the blood vessels to form. Besides forces, the regulation of various types of cell-cell and cell-matrix adhesions is crucial during<unk> . The<unk> astatic steps are critically regulated by various cell types, including the blood vessel cells (endothelial cells), immune cells or stromal cells. The growth of a new network of blood vessels, called tumor angiogenesis, is a crucial hallmark of cancer. It has therefore been suggested that angiogenesis inhibitors would prevent the growth of<unk> . Endothelial progenitor cells have been shown to have a strong influence on<unk>  and angiogenesis. Endothelial progenitor cells are important in tumor growth, angiogenesis and<unk> , and can be marked using the Inhibitor of DNA Binding 1 (ID1). This novel finding meant that investigators gained the ability to track endothelial progenitor cells from the bone marrow to the blood to the tumor-stroma and even incorporated in tumor vasculature. Endothelial progenitor cells incorporated in tumor vasculature suggests that this cell type in blood-vessel development is important in a tumor setting and<unk> . Furthermore, ablation of the endothelial progenitor cells in the bone marrow can lead to a significant decrease in tumor growth and vasculature development. Therefore, endothelial progenitor cells are important in tumor biology and present novel therapeutic targets. The immune system is typically deregulated in cancer and affects many stages of tumor progression, including<unk> . Epigenetic regulation also plays an important role in the<unk> astatic outgrowth of disseminated tumor cells.<unk>  display alterations in histone modifications, such as H3K4-methylation and H3K9-methylation, when compared to matching primary tumors. These epigenetic modifications in<unk>  may allow the proliferation and survival of disseminated tumor cells in distant organs. A recent study shows that PKC-iota promotes melanoma cell invasion by activating Vimentin during EMT. PKC-iota inhibition or knockdown resulted in an increase in E-cadherin and RhoA levels while decreasing total Vimentin, phosphorylated Vimentin (S39) and Par6 in<unk> astatic melanoma cells. These results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma thereby directly stimulates<unk> . Recently, a series of high-profile experiments suggests that the co-option of intercellular cross-talk mediated by exosome vesicles is a critical factor involved in all steps of the invasion-metastasis cascade. Routes<unk>  occurs by the following four routes: Transcoelomic 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. Lymphatic spread Lymphatic spread allows the transport of tumor cells to regional lymph nodes near the primary tumor and ultimately, to other parts of the body. This is called nodal involvement, positive nodes, or regional disease. "Positive nodes" is a term that would be used by medical specialists to describe regional lymph nodes that tested positive for malignancy. It is common medical practice to test by biopsy at least one lymph node near a tumor site when carrying out surgery to examine or remove a tumor. This lymph node is then called a sentinel lymph node. Lymphatic spread is the most common route of initial<unk>  for carcinomas. In contrast, it is uncommon for a sarcoma to<unk> e via this route. Localized spread to regional lymph nodes near the primary tumor is not normally counted as a<unk> , although this is a sign of a worse outcome. The lymphatic system does eventually drain from the thoracic duct and right lymphatic duct into the systemic venous system at the venous angle and into the brachiocephalic veins, and therefore these<unk> astatic cells can also eventually spread through the haematogenous route. Lymph node with almost complete replacement by<unk> astatic melanoma. The brown pigment is focal deposition of melanin Hematogenous spread This is typical route of<unk>  for sarcomas, but it is also the favored route for certain types of carcinoma, such as renal cell carcinoma originating in the kidney and follicular carcinomas of the thyroid. Because of their thinner walls, veins are more frequently invaded than are arteries, and<unk>  tends to follow the pattern of venous flow. That is, hematogenous spread often follows distinct patterns depending on the location of the primary tumor. For example, colorectal cancer spreads primarily through the portal vein to the liver. Canalicular spread Some tumors, especially carcinomas may<unk> e along anatomical canalicular spaces. These spaces include for example the bile ducts, the urinary system, the airways and the subarachnoid space. The process is similar to that of transcoelomic spread. However, often it remains unclear whether simultaneously diagnosed tumors of a canalicular system are one<unk> astatic process or in fact independent tumors caused by the same agent (field cancerization). Organ-specific targets Main sites of<unk>  for some common cancer types. Primary cancers are denoted by "...cancer" and their main<unk>  sites are denoted by "...metastases". There is a propensity for certain tumors to seed in particular organs. This was first discussed as the "seed and soil" theory by Stephen Paget in 1889. The propensity for a<unk> astatic cell to spread to a particular organ is termed 'organotropism'. For example, prostate cancer usually<unk> es to the bones. In a similar manner, colon cancer has a tendency to<unk> e to the liver. Stomach cancer often<unk> es to the ovary in women, when it is called a Krukenberg tumor. According to the "seed and soil" theory, it is difficult for cancer cells to survive outside their region of origin, so in order to<unk> e they must find a location with similar characteristics. For example, breast tumor cells, which gather calcium ions from breast milk,<unk> e to bone tissue, where they can gather calcium ions from bone. Malignant melanoma spreads to the brain, presumably because neural tissue and melanocytes arise from the same cell line in the embryo. In 1928, James Ewing challenged the "seed and soil" theory and proposed that<unk>  occurs purely by anatomic and mechanical routes. This hypothesis has been recently utilized to suggest several hypotheses about the life cycle of circulating tumor cells (CTCs) and to postulate that the patterns of spread could be better understood through a 'filter and flow' perspective. However, contemporary evidences indicate that the primary tumour may dictate organotropic<unk>  by inducing the formation of pre-metastatic niches at distant sites, where incoming<unk> astatic cells may engraft and colonise. Specifically, exosome vesicles secreted by tumours have been shown to home to pre-metastatic sites, where they activate pro-metastatic processes such as angiogenesis and modify the immune contexture, so as to foster a favourable microenvironment for secondary tumour growth.<unk>  and primary cancer It is theorized that<unk>  always coincides with a primary cancer, and, as such, is a tumor that started from a cancer cell or cells in another part of the body. However, over 10% of patients presenting to oncology units will have
Metastasis
Diastasis 
Gliosis
Mixed tumor
Stoma 
Lymphatogenous metastasis
Vascular tumor
Tumor progression