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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

基本信息

批准号：
3174192
负责人：
PAUL B BELL
金额：
$ 6.5万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1988-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3174192
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

项目摘要

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和侵入行为中的接触行为（包括接触抑制）恶性 B16 小鼠黑色素瘤肿瘤细胞。两个替代假设将进行测试以解释肿瘤细胞的侵袭性：（1）它们已经丢失他们对运动的接触抑制的敏感性或（2）他们是能够通过继续前进来避免接触抑制的影响细胞外基质并避免抑制与正常组织的接触细胞。 B16 的变体亚系，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/BL6 小鼠的肺、淋巴结、肠系膜或其他器官，将在体外检查它们的接触行为和侵入性。肿瘤细胞运动、接触行为和接触抑制频率运动将在单层培养物中进行测定，其中群体 B16 细胞面临着正常小鼠细胞群的挑战。一个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技术进行固定培养物中细胞分布的统计分析。这将在小鼠器官培养物中研究 B16 细胞的侵袭行为肠系膜。 B16 不同变异亚系与直接观察肠系膜细胞和细胞外基质，使用延时摄影显微摄影来记录细胞行为。此外，扫描和透射电子显微镜将用于监测侵袭过程并分析侵袭细胞对细胞的影响细胞外基质和肠系膜正常细胞群。数据然后对细胞行为和侵袭进行统计分析与相同侵袭能力的定量数据相关体内细胞亚系，以确定细胞的哪些方面两个和/或三个维度的社会行为要么是积极的，要么是与体内侵袭力呈负相关。 (O)