CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY

自发转化Balb 3T3裸鼠体内接种的研究 细胞研究表明，肿瘤的发展是细胞的问题 社会生物学、生态学和可遗传变异。这一点在 观察到，至少需要1000个细胞才能 引发一种肿瘤，许多这种“低剂量”的肿瘤 发展缓慢，直到出现一次快速增长。这个 序列是肿瘤进展的病原学。相比之下， 均匀接种10/6细胞可迅速而持久地 肿瘤的发展。类似的人口依赖 这些细胞的增殖可以在培养中通过使用 缺乏特定生长因子的培养基，例如，用 作为常规使用的小牛血清的鸡血清。这个 体内和体外情况的相似性表明 增加间质液体的可能性，这是一种滤液 血浆而不是血清，这是 接种在小鼠皮下组织中的细胞，甚至更多 比血浆更缺乏生长因子。肿瘤的发展， 因此，取决于包括细胞在内的微环境 相互作用和细胞中的可遗传变异。我们的计划是 研究所有有助于细胞增殖的因素和 易于量化的细胞状态下的肿瘤进展 文化。将采用替代策略来模拟 间质液生长因子缺乏的环境，包括 血浆、淋巴液和生长组合的使用 商业化无血清限定培养基中使用的因子。这个 鸡血清中特异性缺陷的性质将是 以及不利生长环境对植物生长的影响。 可遗传细胞变异的频率将被测量。一个 将研究细胞之间的相互作用，如果允许 大量细胞在培养基中的快速增殖 缺乏特定的生长因子。任何条件作用于 细胞释放的自分泌生长因子将 特色化的。文化工作将与 裸鼠体内肿瘤生长的定量实验。 其目的是梳理各种过程、因素和 促进肿瘤进展的相互作用 为它的最终控制制定一个理由。

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.