THE ROLE OF CELL MOVEMENT AND CONTACT IN TUMOR INVASION

细胞运动和接触在肿瘤侵袭中的作用

• 批准号: 3174191
• 负责人: PAUL B BELL
• 金额: $ 6.7万
• 依托单位: UNIVERSITY OF OKLAHOMA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174191
• 关键词: cell cell interaction; cell growth regulation; cell migration; cell motility; cinematography; contact inhibition; electron microscopy; extracellular matrix; mesentery; neoplasm /cancer invasiveness; neoplastic cell; neoplastic growth; organ culture; photomicrography; scanning electron microscopy

The goal of this study is to elucidate the role of cell movement and contact behavior (including contact inhibition) in the invasive behavior of malignant B16 murine melanoma tumor cells. Two alternative hypotheses will be tested to explain tumor cell invasiveness: (1) that they have lost their susceptibility to contact inhibition of movement or (2) that they are able to avoid the effects of contact inhibition by moving on available extracellular substrata and avoiding inhibiting contacts with normal tissue cells. Variant sublines of B16, which exhibit quantitative differences in their ability to invade locally into tissues and to metastasize to the lungs, lymph nodes, mesentery, or other organs of syngeneic C57/BL6 mice, will be examined for their contact behavior and invasiveness in vitro. Tumor cell motility, contact behavior, and frequency of contact inhibition of movement will be assayed in monolayer cultures in which populations of B16 cells are confronted with populations of normal murine cells. A qualitative and quantitative analysis of cell movement and contact behavior will be carried out using time lapse cinemicrography of living cells and statistical analysis of the distribution of cells in fixed cultures. The invasive behavior of B16 cells will be studied in organ cultures of murine mesentery. The interactions of different variant sublines of B16 with the cells and extracellular matrix of the mesentery will be observed directly, using time lapse cinemicrography to record cell behavior. In addition, scanning and transmission electron microscopy will be used to monitor the process of invasion and to analyze the effects of invading cells on the extracellular matrix and normal cell population of the mesentery. The data on cell behavior and invasion will then be analyzed statistically and correlated with quantitative data on the invasive ability of the same subline of cells in vivo, in order to determine which aspects of cell social behavior in two and/or three dimensions are either positively or negatively correlated with invasiveness in vivo. (O)

本研究的目的是阐明细胞运动的作用， 接触行为（包括接触抑制）的侵入行为， 恶性B16小鼠黑色素瘤细胞。 两个备选假设将 被测试来解释肿瘤细胞的侵袭性：（1）他们已经失去了 他们对运动接触抑制的敏感性或（2）他们是 能够避免接触抑制的影响， 细胞外基质和避免抑制与正常组织的接触 细胞 B16的变体亚系，其在以下方面表现出数量差异： 它们能够局部侵入组织并转移到 同系C57/BL 6小鼠的肺、淋巴结、肠系膜或其它器官， 将检查它们的接触行为和体外侵袭性。 肿瘤细胞运动性、接触行为和接触抑制频率 将在单层培养物中测定运动的能力， B16细胞与正常鼠细胞群相遇。 一 细胞运动和接触行为的定性和定量分析 将使用活细胞的延时电影显微摄影进行， 固定培养物中细胞分布的统计分析。 的 将在小鼠器官培养物中研究B16细胞的侵袭行为 肠系膜 B16的不同变异亚系与细胞的相互作用 将直接观察肠系膜的细胞和细胞外基质， 使用延时电影显微摄影术来记录细胞行为。 此外，本发明还提供了一种方法， 扫描和透射电子显微镜将用于监测 探讨了细胞的侵袭过程，并分析了侵袭细胞对肿瘤细胞的影响。 细胞外基质和肠系膜的正常细胞群。 数据 对细胞行为和侵袭的影响进行统计分析， 相关的定量数据的侵入能力， 细胞亚系，以确定哪些方面的细胞 社会行为在两个和/或三个方面是积极的， 与体内侵袭性呈负相关。 （O）