Hepatocyte growth factor in invasive growth of carcinomas.
Hepatocyte growth factor is a multifunctional cytokine of the tumor microenvironment. An important advance in the knowledge of cancer progression has been the appreciation that the tumor invasive phenotype is strongly influenced by microenvironmental stimuli. Malignant tumor cells recruit vasculature and stroma through the production of growth factors and cytokines. The locally activated microenvironment (both cellular and extracellular elements) in turn modifies the proliferative and invasive behavior of the tumor cells. Hepatocyte growth factor accomplishes most of the functions of the invasive program in carcinomas (loss of adhesive junctions, motility, angiogenesis, survival/apoptosis), and may interact with other signals such as hypoxia. The purpose of the present review is to highlight examples of the progress in this area. The influence of hepatocyte growth factors on the carcinoma invasive phenotype is considered by evaluating the gene targets and the network of transcription factors activated in the specific responses.
Desiderio
M A
MA
Institute of General Pathology, School of Medicine, University of Milan, via Luigi Mangiagalli, 31-20133, Milan, Italy. a.desiderio@unimi.it
D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D010641:Phenotype; D010958:Plasminogen / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D015820:Cadherins; D051793:Hypoxia-Inducible Factor 1; D019707:Receptors, Chemokine; D051880:Receptors, Notch; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D010958:Plasminogen; D019859:Proto-Oncogene Proteins c-met; D020782:Matrix Metalloproteinases