[When and why does cancer metastasize? An overview of current viewpoints OF the molecular mechanism of invasiveness].
Invasion is the cause of cancer malignancy. Invasion leads to metastasis and metastases turn cancer into an incurable disease. The only model of "true" invasion and metastasis is the natural human or animal tumor. Nevertheless, experimental models have largely contributed to the development of new concepts such as the multistep invasion process of metastasis, the growth-separate-from-invasion concept and the transient expression of the invasive phenotype by a subpopulation of cancer cells. All these aspects of invasion are considered within micro-ecosystems that are initiated by the cancer cells but in which host cells may play an equally important role. It is our opinion that invasion is regulated by the balance between the activation and inactivation of two sets of genes, invasion-promoter and invasion-suppressor genes. These genes encode molecules that determine the expression of the invasive and the noninvasive (normal) phenotype. E-cadherin is an invasion-suppressor gene product that belongs to the calcium-dependent homophilic cell-cell adhesion molecules. This transmembrane glycoprotein is involved not only in the mechanics of adhesion but also serves as a signal-transducer via its linkage with the catenins and the actin cytoskeleton. In human and in experimental cancers disturbance of the cadherin-catenin complex have been found at multiple levels. Candidate invasion-promoter molecules may be found among lytic enzymes and their associated molecules, motility factors and heterotypic cell-cell adhesion molecules. Investigation of the cellular interactions within the micro-ecosystem of bone metastasis has lead to the treatment of bone metastases with bisphosphonates. This application demonstrates the potential clinical benefit of a better understanding of the cellular and molecular mechanisms of cancer invasion and metastasis.
Mareel
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Laboratorium voor Experimentele Cancerologie, Vakgroep Radiotherapie, Kerngeneeskunde en Experimentele Cancerologie, Gent.
D000818:Animals; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology*; D009369:Neoplasms / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics / Q000503:physiopathology; D014407:Tumor Cells, Cultured
Wanneer en waarom metastaseert kanker? Een overzicht van recente inzichten in de moleculaire mechanismen van invasie.