Movement of human mammary tumour cells in culture: exclusion of fibroblasts by epithelial territories.

Time-lapse cinematography was used to investigate the movement of confronting populations of human mammary epithelium and stromal cells (fibroblasts). Epithelial cell islands from fibroadenomas and from normal lacteal secretions completely excluded the fibroblasts, and individual cell territories were maintained even in dense cultures. Electron microscopy of the boundary between epithelium and fibroblasts showed that the two cell types made contact. In contrast, epithelial islands from two carcinomas did not retain territorial integrity and allowed penetration of mammary fibroblasts. Confronting homologous eptihelial islands from benign tumours merged, but this was shown to be due to interdigitation rather than free mixing of cell. Epithelial cells moved actively but unlike fibroblasts they retained their neighbour relationships.

The multiplication of cells.

Cultured cells, particularly fibroblasts, have been useful for studies on control systems, since growth can be stimulated or suppressed experimentally. Combinations of mitogenic factors (hormones) in the extracellular fluid, provide positive signals for growth, potentially acting over a long range. Short range effects, such as cell-cell interactions and anchorage to substrates, also control growth but these are less well understood. A positive signal for growth, for example the binding of a mitogenic polypeptide factor to a surface receptor, leads rapidly to a complex change in cell physiology, which can be explained by an alteration of mobile cell surface complexes. This leads to an increase in probability, not certainty, of transition through an essential control point leading to chromosome replication and mitosis.

Growth requirements of human mammary epithelial cells in culture.

Colony-forming epithelial cells can be separated from the non-dividing "foam cells" in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co-culture with non-dividing feeder cells. Foam cells, mitomycin-treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth-promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.

Conditions determining initiation of DNA synthesis in 3T3 cells.

Experiments were designed to discriminate between inhibition of growth due to contacts or exhaustion of serum factors. The cell layer was wounded and the migrating cells were followed by time-lapse cinematography; DNA synthesis in the same cells was recognized by means of (3)H-thymidine labeling and radioautography. In this way, the complete history of individual cells migrating to the wound could be described. The results show that topographical relationships between cells play an important role in controlling initiation of DNA synthesis. It is still unclear whether initiation is promoted by release from contacts or by the increased ability of the cells to utilize serum factors because of their changes in shapes and activities.