INTERACTIONS BETWEEN SCATTER FACTORS AND THEIR RECEPTORS - HINTS FOR THERAPEUTIC APPLICATIONS

The scatter factors, which include hepatocyte growth factor and macrop hage stimulating protein, stand out from other cytokines because of th eir uncommon biological properties. In addition to promoting cell grow th and protection from apoptosis, they are involved in the control of cell dissociation, migration into extracellular matrices, and a unique process of differentiation called 'branching morphogenesis'. Through the concerted regulation of these complex phenomena, scatter factors p romote development, regeneration, and reconstruction of normal organ a rchitecture. In transformed epithelia, scatter factors can mediate tum or invasive growth, a harmful feature of neoplastic progression in whi ch cancer cells invade surrounding tissues, penetrate across the vascu lar walls, and eventually disseminate throughout the body, giving rise to systemic metastases. A much-debated issue in basic biology, which has strong implications for experimental medicine, is how to dissociat e the favorable effects of growth factors from their adverse ones. Acc ordingly, to find agonists or antagonists with potential therapeutic a pplications is a crucial undertaking for current research. Domain-mapp ing analyses of growth factor molecules can help to isolate specific s tructural requirements for the induction of selective biological effec ts. Based on the observation that certain growth factors must undergo posttranslational modifications to exert a full response, it is possib le to interfere with their activation mechanisms to modulate their fun ctions. Finally, the identification of cell type-specific coreceptors able to potentiate their activity allows drawing of a functional body map, where some organs or tissues may be more responsive than others t o growth factors. This review is focused on how, and to what extent, s catter factors can behave 'well' or 'badly' according to their molecul ar structure, the way they are activated, and the way they interact wi th cell surface receptors and coreceptors.