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Most cancer morbidity and mortality occurs upon spread of the tumorfrom an original localized site. Primary tumors are, by and large, accessiblefor surgical removal or radiological eliminaTIon. However, once the tumorextends beyond the physiological borders, these approaches are eitherrendered ineffecTIve or engender significant morbidity and mortality inthemselves. Subsequent therapeuTIcs suffer from the need to be globally orbroadly applied with the concomitant toxiciTIes. Limiting this disseminationwould provide palliative benefit, improve physical targeting of cytotoxictherapies, or just stabilize the tumor in a manageable state. Therefore, suchlimitation of tumor dissemination per se is an appropriate goal for newtherapies. However, to realize this in a rational and targeted manner, tumorcell behaviors that enable dissemination must be defined and their keymolecular controls identified.Tumor dissemination takes two forms, invasion and metastasis (Table 1).Localized invasion of unaffected tissue and adnexia compromises normalhomeostatic functions of the organs. This invasion is distinct from noninvasivebut otherwise growing localized tumors in that the invasive tumorcells breach physiologic boundries and/or organ capsules to interdigitatewith normal cells. That this ability is not simply related to cell proliferationwas evident when it was noted that the growth rate of invasive tumors wasnot appreciably greater than encapsulated counterparts (1). A number of cellproperties were examined as the basis for this contiguous spread. Inducedcell motility has come to be recognized as the dominant regulator of tumorinvasion (2), particularly as matrix degradation and remodeling is nowunderstood to be limited rather than extensive, and a part of or partner tomotility (3, 4) (see Chapter 7).
