CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY

将自发转化的Balb 3 T3接种到裸鼠中 细胞已经揭示，肿瘤的发展是一个细胞的问题， 社会生物学、生态学和遗传变异。 这表现在 观察到至少需要1000个细胞， 引发肿瘤，许多这样的“低剂量”肿瘤 缓慢发展直到突然快速增长。 的 序列是肿瘤进展的特异性标志。 相比之下， 接种10/6细胞均匀地导致快速和持续的 肿瘤的发展。 类似的人口依赖 这些细胞的增殖可以通过使用 缺乏特定生长因子的培养基，例如，通过替换 用鸡血清代替常规使用的小牛血清。 的 体内和体外情况之间的相似性已经指出， 增加了组织液（即组织液的滤液） 血浆而不是血清，它作为培养基， 接种在小鼠皮下组织中的细胞，甚至更多 比血浆缺乏生长因子。 肿瘤发展， 因此，这取决于微环境， 相互作用和细胞中的遗传变异。 我们的计划是 研究所有有助于细胞增殖的因素， 在细胞易于量化的情况下肿瘤进展 文化 将应用替代策略来模拟 间质液的生长因子缺乏环境，包括 使用血浆、淋巴液和生长因子的组合 商业无血清确定培养基中使用的因子。 的 鸡血清中特异性缺乏的性质将是 阐明，不利的生长环境对 将测量可遗传细胞变异的频率。 一 将研究细胞之间的相互作用， 大量细胞在培养基中的快速增殖 缺乏特定的生长因子。 任何条件反射 由细胞释放的自分泌生长因子将 表征了 文化工作将与 裸鼠肿瘤发展的定量实验。 目的是梳理各种过程、因素和 促进肿瘤进展的相互作用 为最终的控制制定一个合理的解释。

Inoculation into nude mice of spontaneously transformed Balb 3T3 cells has revealed that tumor development is a problem of cellular sociobiology, ecology and heritable variation. This is manifest in the observations that a minimum of 1000 cells is required to initiate a tumor and many such "low dose" tumors are inordinately slow in development until a burst of rapid growth occurs. The sequence is pathognomonic of tumor progression. By contrast, the innoculation of 10/6 cells uniformly results in rapid and sustained development of tumors. A similar population dependent multiplication of these cells can be produced in culture by using a medium deficient in specific growth factors, e.g., by substituting chicken serum for the conventionally used calf serum. The similarity between the in vivo and in vitro situations has pointed up the likelihood that the interstitial fluid, which is a filtrate of plasma rather than serum, and which serves as the medium for cells inoculated in subcutaneous tissue of the mouse, is even more deficient in growth factors than is plasma. Tumor development, therefore, depends on the microenvironment including cellular interactions and on heritable variation in the cells. Our plan is to study all the factors which contribute to cell multiplication and tumor progression in the easily quantified situation of cell culture. Alternative strategies will be applied for simulating the growth factor deficient environment of interstitial fluid, including the use of plasma, lymphatic fluid and combinations of growth factors used in commercial serum- free defined medium. The nature of the specific deficiency in chicken serum will be elucidated, and the effect of unfavorable growth environments on the frequency of heritable cell variation will be measured. A study will be made of the interactions among cells which permit rapid multiplication of large numbers of cells in a medium deficient in specific growth factors. Any conditioning on autocrine growth factors released by the cells will be characterized. The work in culture will be coordinated with quantitative experiments on tumor development in nude mice. The aim is to sort out the various processes, factors and interactions which contribute to tumor progression and thereby develop a rationale for its eventual control.