| Research Abstract |
We recently proposed that most mammalian cells other than blastomeres may be programd to kill themselves unless continuously signaled by other cells not to. As it is impractical to test all of the hundreds of types of mammalian cells, we first tested two tissues--lens and cartilage--which each contain only a single cell type : if there are cells that do not require signals from other cells to avoid programd cell death (PCD), lens epithelial cells and cartilage cells (chondrocytes) might be expected to be among them. We had previously shown that rat lens epithelial cells can survive in serum-free culrute without signals from other cell types but seem to require signals from other lens epithelial cells to survive : without such signals they undergo PCD.We found that the same is true for rat (and chick) chondrocytes. They can survive for weeks in culture at high cell density in the absence of other cell types, serum, or exogenous proteins or signaling molecules, but they die with the morp
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hological features of apopotosis in these conditions at low cell density. Medium from high density cultures, FCS,or a combination of known growth factors, all support prolonged chondrocyte survival in low density cultures, as long as antioxidants are also present. Moreover, medium from high density chondrocyte cultures promotes the survival of lens epithelial cells in low density cultures and vice versa. Chondrocytes isolated from adult rats behave similarly to those isolated from devoloping rats. These findings support the hypothesis that most mammalian cells require signals from other cells to avoid PCD,although the signals can sometimes be provided by cells of the same type, at least in tissues that contain only one cell type. We also tested purified fibroblasts isolated from developing or adult rat sciatic nerve, a, mixture of cell types isolated from normal or p53 null mouse embryos, an immortalized rat fibroblast cell line, and a number of cancer cell lines. We find the following : (1) All of these cells undergo PCD when cultured at low cell density in the absence of serum and exogenous signaling molecules but can be rescued by serum or specific growth factors, suggesting that they need extracellular signals to avoid PCD.(2) The mixed cell types dissociated from normal mouse embryos can only support one another's survival in culture if they are in aggregates, suggesting that cell survival in embryos may depend on short-range signals. (3) Some cancer cells secrete factors that support their own survival. (4) The survival requirements of a human leukemia cell line change when the cells differentiate. (5) All of the cells studied can undergo PCD in the presence of cycloheximide, suggesting that they constitutively express all of the protein components required to execute the death program. Less
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