The propagation of cancer, a process of tissue remodeling. Studies in histophysiologic gradient culture

Effective study of the malignant phenotype at the tissue level requires model systems that are intelligible both to cell biologists and to pathologists, and that also observe the spatial imperatives intrinsic to tissues in nature. Malignant cells commonly appear in multicellular units, and growth of tumor tissue is seen as an increase in the number of cells and multicellular units. The supporting stroma frequently has an abnormal appearance, and this component of the tissue also increases in mass as the tumor enlarges and spreads. The direction of invasion is influenced by the direction of available metabolites. Histophysiologic gradient culture complies with nature's spatial rationale, since at the substrate-parenchymal interface three functions coincide. These are anchorage, initiation of epithelial renewal, and complete exchange of metabolites. Our model system provides a setting for reconstructing and manipulating many features of the malignant phenotype seen in cancer tissues in nature, such as abnormalities in the sequence of maturation of stratified epithelium, hyperplasias, dysplasias, interaction between different types of epithelium, aggregate formation, tumor angiogenesis, and neoplastic blockade.