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Genetically modified mouse models of cancer invasion and metastasis

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Tumor progression is associated with distinct histopathological changes that are indicative for prognosis. The acquired ability of tumor cells to locally invade adjacent tissues is the first important step in the invasion-metastasis cascade. Two general strategies have been pursued in mice to investigate invasive tumor progression.

The first strategy uses GEMMs that are suitable for the investigation of early steps in cancer invasion but infrequently give rise to distant metastases. The second strategy uses transplantation of tumor cells or tumor tissue into host mice and is employed to study early invasiveness but also later stages such as entering and leaving the blood stream. Increasingly GEMMs have been used in recent years to understand the major mechanisms underlying invasion and metastasis in humans and for the evaluation of antimetastatic drug treatments. While syngeneic and xenograft models using human cancer cells transplanted into host mice might still provide the method of choice to investigate far distant metastasis or to apply drug treatments. At present, GEMMs are more commonly used for the investigation of tumor initiation or local invasiveness because metastasis occurs infrequently or is restricted to lymph nodes and lung. However, recently established mouse models for metastasizing prostate and lung cancer nourish the hope that GEMMs with comparable metastasis rates and tropisms to human cancers will be developed which are of preclinical relevance.

Emilio Casanova and colleagues have reviewed recently the use of genetically engineered mice for the research into metastatic processes, which has been published at Drug Discovery Today: Disease Models, from where the figure is taken.