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MetastasisMetastasis, a major determinant of cancer fatality, is a complex, multistep and multifactorial process which often allows the dissemination of cancer cells from a primary tumor to distant tissues and organs leading to the establishment of secondary tumors. The metastatic process is first facilitated by cellular proliferation within primary lesions which results in tumor invasion through adjacent epithelium and basement membranes. This initial phase ultimately allows cells that detach from the primary tumor to migrate to nearby tissues or into blood and lymphatic vessels to reach secondary tissues where they may adhere and grow. Metastasis Cascade and Mechanisms of Suppression
Metastasis suppressors prevent the establishment of cancer growth in secondary tissues without affecting growth of primary tumors. Molecules halting metastatic growth may act via a broad range of mechanisms including effects on cell adhesion properties, signaling pathways important for cell motility and survival, and transcription of genes with pro-metastatic potential. The ability of primary tumor cells to become invasive is partly determined by the intrinsic expression and function of metastasis promoters and suppressors. The genetic basis of metastasis has been a key focus of cancer research leading to the identification of over 30 metastasis suppressors which are defined by their ability to prevent cancer spread without affecting primary tumor growth. However, extrinsic factors such as the tumor microenvironment have increasingly gained attention due to the crucial role of stromal cells and derived factors in the establishment of secondary tumors. Metastatic potential is not only influenced by the primary tumor’s microenvironment, but is also dependent on the cells and factors present at secondary targeted tissues. Validated Metastasis Suppressors
*https://www.cancer.gov/types/metastatic-cancer
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