Tucker R W, Butterfield C E, Folkman J
J Supramol Struct Cell Biochem. 1981;15(1):29-40. doi: 10.1002/jsscb.1981.380150104.
Both growth factor availability and cell-to-cell contact have been mechanisms used to explain cell growth regulation at high cell density. Recently Folkman and colleagues have shown that changes in cell shape, rather than cell-to-cell contact, can regulate the growth of fibroblasts. However, in those studies the relation between serum and shape regulation of growth was not studied, nor were neoplastic and non-neoplastic cells compared. In this report we have studied these aspects by varying cell spreading and serum concentration independently for 2 non-neoplastic and 3 neoplastic cell lines. Cell spreading (projected cell area) was controlled by decreasing the adhesiveness of tissue culture growth was measured as the increase in cell number/day. We have found that more spreading increased net growth of both neoplastic and non-neoplastic cells, while less spreading (toward rounded configuration) depressed growth. There were also quantitative differences between neoplastic and non-neoplastic cells. Neoplastic cells continued to grow under conditions of cell rounding, which completely prevented the growth of their non-neoplastic counterparts. Some neoplastic cells also tended to show little or no increase in net cell number for serum concentrations above 10% as cells became more spread; in contrast, all non-neoplastic cells grew more with increasing concentrations of serum as they became well spread. Thus, in normal cells, it appears that the sensitivity of cells to humoral factors is governed by cell spreading. This interaction between serum and cell shape is less prominent in some neoplastic cells.
生长因子的可获得性和细胞间接触都曾被用作解释高细胞密度下细胞生长调控的机制。最近，福克曼及其同事表明，细胞形状的改变而非细胞间接触能够调节成纤维细胞的生长。然而，在那些研究中，血清与生长的形状调控之间的关系并未被研究，肿瘤细胞和非肿瘤细胞也未进行比较。在本报告中，我们通过独立改变2种非肿瘤细胞系和3种肿瘤细胞系的细胞铺展程度及血清浓度，对这些方面进行了研究。细胞铺展（细胞投影面积）通过降低组织培养的黏附性来控制，生长则以细胞数量/天的增加来衡量。我们发现，铺展程度越高，肿瘤细胞和非肿瘤细胞的净生长就越多，而铺展程度越低（趋向圆形形态），生长则受到抑制。肿瘤细胞和非肿瘤细胞之间也存在定量差异。在细胞变圆的情况下，肿瘤细胞仍能继续生长，而这完全抑制了其非肿瘤对应细胞的生长。随着细胞铺展程度增加，一些肿瘤细胞在血清浓度高于10%时，净细胞数量也往往几乎没有增加或没有增加；相反，所有非肿瘤细胞在铺展良好时，随着血清浓度升高生长得更多。因此，在正常细胞中，细胞对体液因子的敏感性似乎受细胞铺展的支配。血清与细胞形状之间的这种相互作用在一些肿瘤细胞中不太明显。
