CELLULAR ADAPTATION AND PROGRESSION TO MALIGNANCY

细胞适应和恶性肿瘤进展

• 批准号: 3164263
• 负责人: HARRY RUBIN
• 金额: $ 17.19万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-08-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164263
• 关键词: athymic mouse; cell cell interaction; cell differentiation; deficient growth media; growth factor; histochemistry /cytochemistry; neoplasm /cancer transplantation; neoplastic cell; neoplastic growth; neoplastic transformation; serum; tissue /cell culture

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.

自发转化Balb 3T3裸鼠接种 细胞研究揭示肿瘤的发生是细胞的问题 社会生物学、生态学和遗传变异。 这体现在 至少需要 1000 个细胞才能观察到 引发肿瘤，许多此类“低剂量”肿瘤异常严重 发展缓慢，直到爆发性的快速增长。 这 序列是肿瘤进展的特征。 相比之下， 10/6 细胞均匀接种可导致快速且持续的结果 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 培养基缺乏特定的生长因子，例如，通过替代 鸡血清为常规使用的小牛血清。 这 体内和体外情况的相似性表明 间质液（滤液）的可能性增加 血浆而不是血清，并作为介质 将细胞接种到小鼠皮下组织中，效果更佳 与血浆相比，生长因子缺乏。 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 在易于量化的细胞情况下肿瘤进展 文化。 将应用替代策略来模拟 生长因子缺乏的间质液环境，包括 血浆、淋巴液的使用和生长的组合 商业无血清成分确定培养基中使用的因子。 这 鸡血清中特定缺乏症的性质将是 阐明了不利的生长环境对 将测量可遗传细胞变异的频率。 一个 将研究细胞之间的相互作用，从而允许 大量细胞在培养基中快速增殖 缺乏特定的生长因子。 任何调节 细胞释放的自分泌生长因子 特点。 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，从而 为其最终控制制定一个理由。