Molecular mechanisms of cancer metastasis: tumor and host properties and the role of oncogenes and suppressor genes.
The natural progression of benign tumors to malignancy and metastasis is characterized by their ability to circumvent microenvironmental controls on cellular proliferation, diversity, and positioning, and evolve into heterogeneous phenotypes, a process that probably involves qualitative and quantitative changes in gene expression. The oncogenes and suppressor genes that can effect tumor progression may control important points in the regulation of sets of genes that are ultimately responsible for the cellular alterations seen in highly metastatic cells. Because many cancers metastasize nonrandomly to particular distant sites, their colonization properties cannot be explained by mechanical considerations, such as arrest of tumor cells in the first microcirculatory network encountered. Metastatic cells that show a high propensity to metastasize to certain organs adhere at higher rates to microvessel endothelial cells isolated from their target sites, invade into target tissue at higher rates, and respond better to paracrine growth factors from the target site. These properties depend on multiple tumor cell, host cell, and stromal molecules that are differentially expressed by particular tumor and organ cells and by the organ extracellular matrix. Together these tumor and host factors appear to determine the organ metastatic properties of malignant cells.
Nicolson
G L
GL
University of Texas M.D. Anderson Cancer Center, Houston.
D000595:Amino Acid Sequence; D001485:Basement Membrane / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D009857:Oncogenes; D009928:Organ Specificity
D015815:Cell Adhesion Molecules; D006133:Growth Substances; D009363:Neoplasm Proteins