Self-regulation of growth in three dimensions.
Self-regulation of growth in three dimensions.
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DOI：
10.1084/jem.138.4.745
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发表时间：
1973-10-01
期刊：
影响因子：
--
通讯作者：
Hochberg M
中科院分区：
文献类型：
--
作者：
Folkman J;Hochberg M
当在大量的培养基中培养每个球形的琼脂中，多细胞球形的球形植物最终在大约3-4 mm的直径和大约106个细胞的直径上培养休眠的球体，在周围的新产生的细胞平衡了中心坏死的人。体积：尺寸超出了面积，可以消除分解代谢物并吸收营养，这在面对无限的空间和新培养基的情况下，三维细胞与这种现象形成鲜明对比。标准的组织培养物，在二维中生活在平坦平面上的细胞群不会在面对无限空间和新培养基的情况下停止生长，因为表面积之比量保持恒定，这些实验为我们的体内观察提供了一种机制：在血管化之前，通过简单的扩散来生存，因为三维球体或椭圆形会在几毫米的直径上处于休眠状态。从该休眠期释放，并开始指数生长。负责体外球体的休眠状态。
Multi-cell spheroids were grown in soft agar. When each spheroid was cultured in a large volume of medium, frequently renewed, all spheroids eventually reached a dormant phase at a diameter of approximately 3–4 mm and a population of approximately 106 cells. In the dormant spheroid, newly generated cells at the periphery balanced those lost by necrosis in the center. We propose that this dormant phase is due to a gradual reduction in the ratio of surface area to volume: a size is achieved beyond which there is insufficient surface area for the spheroid to eliminate catabolites and absorb nutrients. Thus, in the face of unlimited space and of new medium, three-dimensional cell populations become self-regulating. This phenomenon contrasts with standard tissue culture in which cell populations, living on a flat plane in two dimensions, will not stop growing in the face of unlimited space and new medium because the ratio of surface area to volume remains constant. These experiments provide a mechanism for our observations in vivo: before vascularization, solid tumors live by simple diffusion as three-dimensional spheroids or ellipsoids. They become dormant at a diameter of only a few millimeters; once vascularized, they are released from this dormant phase and begin exponential growth. Thus, tumor dormancy resulting from absence of angiogenesis in vivo, may operate by the same mechanism responsible for dormancy of spheroids in vitro.