Interactions between scatter factors and their receptors: hints for therapeutic applications. 1998

L Trusolino, and L Pugliese, and P M Comoglio
Division of Molecular Oncology, IRCC, Institute for Cancer Research, University of Torino School of Medicine, 10060 Candiolo, Torino, Italy.pcomoglio@ircc.unito.it

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.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009102 Multiple Organ Failure A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. MODS,Multiple Organ Dysfunction Syndrome,Organ Dysfunction Syndrome, Multiple,Organ Failure, Multiple,Failure, Multiple Organ,Multiple Organ Failures
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell

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