Steps in Metastasis

The formation of metastasis is a multistep process involving a number of linked sequential events (F5). The main steps are as follows  

Interaction of tumor cells in circulation with fibrin and platelets, 

Extravasation of tumor cells through blood vessel wall into secondary organ, and 

It is important to state that not all malignant tumors give rise to metastases. Basal cell carcinoma of the skin, while capable of local invasion, rarely produces secondary growths. However, most other cancers give rise to metastases at some 

Three main routes exist for the spread of cancer cells throughout the body. These involve the lymphatic system, the blood system, and direct extension into body cavities. Spread by the lymphatic system is thought to be important for carcinomas. The walls of these channels offer little mechanical resistance to penetration by tumor cells. Malignant cells readily invade the walls of these vessels and are carried to regional lymph nodes. In the lymph node, the cancer cells can arrest, proliferate and produce a metastatic tumor. Malignant cells may later detach from the lymph node and be carried in the bloodstream to other sites throughout the body. 

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Metastasis is an inefficient process because it consists of multiple and complex steps, all of which must be successfully completed to give rise to the formation of metastatic tumors [12]. Recent studies suggest that the least-efficient steps in metastasis are the survival and growth of the micrometastatic foci and their... 

Formation of regional lymph node metastasis can be an important step in dissemination of cancer cells. In colorectal cancer, lymph node metastasis frequently occurs in patients (7, 8) and is an important factor in staging the disease. In particular, the metastatic lymph node ratio (LNR number of metastatic lymph nodes/number of examined lymph nodes) is predictive of overall survival (OS) and disease-free survival (DFS) in colorectal cancer patients (9, 10). Hence, an animal model of colorectal cancer with measurable lymphatic metastasis that allows for rapid evaluation of the effects of candidate treatment regimens on primary tumor growth and lymph node metastasis would be of great value. 

Metastasis is not equivalent to invasion, adhesion, growth rate, susceptibility to immune cell killing, or any of the many steps in the metastatic cascade. These processes are necessary for successful colonization of secondary sites, but they are not sufficient for a cell to be metastatic. Failure to distinguish between individual steps from the complete process of metastasis has contributed greatly to confusion and misinterpretation in the scientific literature. Just because a cell line is highly invasive or adheres strongly to extracellular matrices does not necessarily translate to its having the ability to metastasize. Yet, this type of faulty extrapolation is common. 

Morris, V. L., Schmidt, E. E., MacDonald, I. C., Groom, A. C. and Chambers, A. F. (1997). Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy. Invasion Metastasis 17, 281-296. 

Saidel et al. (1975) developed a lumped parameter, deterministic model to describe these five steps in the metastatic process. This model describes their data on pulmonary metastatic formation from a fibrosarcoma implanted in mice and simulates the effects of various perturbations (e.g., external tumor massage, primary tumor amputations) on metastatic process. These authors also developed a stochastic model of metastasis... 

Chambers AF, MacDonald IC, Schmidt EE, Koop S, Morris VL, Khokha R, Groom AC. Steps in tumor metastasis new concepts from intravital videomicroscopy. Cancer Metastasis Rev 1995 14 279-301. 

Metastasis to regional lymph nodes is a common step in tumor progression. Earlier study showed a contributory role of NO in tumor metastasis using experimental tumor models (Edwards et al. 1996). Recent evidence by Yasuoka et al. showed that incubation of K1 and B-CPAP PTC cells with an NO donor resulted in induction of functional CXCR4 expression in a NO-dependent manner (Yasuoka et al. 2008). 

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