Interactions between scatter factors and their receptors: hints for therapeutic applications.
The scatter factors, which include hepatocyte growth factor and macrophage stimulating protein, stand out from other cytokines because of their uncommon biological properties. In addition to promoting cell growth 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 promote development, regeneration, and reconstruction of normal organ architecture. In transformed epithelia, scatter factors can mediate tumor invasive growth, a harmful feature of neoplastic progression in which cancer cells invade surrounding tissues, penetrate across the vascular 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 dissociate the favorable effects of growth factors from their adverse ones. Accordingly, to find agonists or antagonists with potential therapeutic applications is a crucial undertaking for current research. Domain-mapping analyses of growth factor molecules can help to isolate specific structural requirements for the induction of selective biological effects. Based on the observation that certain growth factors must undergo posttranslational modifications to exert a full response, it is possible to interfere with their activation mechanisms to modulate their functions. 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 to growth factors. This review is focused on how, and to what extent, scatter factors can behave 'well' or 'badly' according to their molecular structure, the way they are activated, and the way they interact with cell surface receptors and coreceptors.
Trusolino
L
L
Division of Molecular Oncology, IRCC, Institute for Cancer Research, University of Torino School of Medicine, 10060 Candiolo, Torino, Italy.pcomoglio@ircc.unito.it
Pugliese
L
L
Comoglio
P M
PM
D000595:Amino Acid Sequence; D005326:Fetal Proteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D018082:Kringles; D008954:Models, Biological; D008969:Molecular Sequence Data; D009102:Multiple Organ Failure / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D011487:Protein Conformation; D011509:Proteoglycans / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017385:Sequence Homology; D012697:Serine Endopeptidases / Q000737:chemistry; D015398:Signal Transduction
D005326:Fetal Proteins; D006025:Glycosaminoglycans; D006133:Growth Substances; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; D012697:Serine Endopeptidases