TUMOR-CELL HETEROGENEITY - DIVIDED-COLONY ASSAY FOR MEASURING DRUG RESPONSE
TUMOR-CELL HETEROGENEITY - DIVIDED-COLONY ASSAY FOR MEASURING DRUG RESPONSE
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DOI：
10.1073/pnas.84.13.4490
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
AXELROD, DE
中科院分区：
文献类型：
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作者：
KUCZEK, T;AXELROD, DE
预测肿瘤对化疗药物反应的体外试验如果考虑到肿瘤细胞的异质性而加以修改，可能会得到改进。我们研究了小鼠成纤维细胞NIH 3 T3细胞和用来自EJ人膀胱癌细胞系的人H-RAS基因（哈维肉瘤病毒癌基因v-Ha-ras的同源物）转化的NIH 3 T3细胞中细胞生长速率和药物反应的异质性。生长速率异质性检测为每个集落细胞数的广泛分布。尽管存在这种异质性，但次级集落的每个集落的细胞数与它们所来源的初级集落的细胞数相似。H-RASEJ增加了不相关的次级菌落之间的方差。菌落大小测量是可靠的，因为分成两半的初级菌落形成了两组次级菌落（在两个单独的平板上），其具有不可区分的平均菌落大小。基于这些观察结果，设计了一种分集落程序来检测异质细胞群的药物反应。将原代集落分成两组细胞，其中一组用药物处理，另一组不处理作为对照。然后将处理的次级菌落的大小分布与未处理的对照和其来源的初级菌落的大小分布进行比较。提出了分割集落程序作为人肿瘤集落系统的修改，以增加用于确定异质性肿瘤细胞群体的药物反应的体外程序的灵敏度和可靠性。
In vitro tests for predicting the response of tumors to chemotherapeutic agents might be improved if they were modified to take into account tumor-cell heterogeneity. We have studied the heterogeneity of cellular growth rate and drug response in mouse fibroblast NIH 3T3 cells and in NIH 3T3 cells transformed with the human H-RAS gene (homologue of the Harvey sarcoma virus oncogene v-Ha-ras) from the EJ human bladder carcinoma cell line. Groth-rate heterogeneity was detected as a broad distribution of number of cells per colony. In spite of this heterogeneity, secondary colonies have numbers of cells per colony that resemble that of the primary colony from which they were derived. The variance between unrelated secondary colonies is increased by H-RASEJ. Colony-size measurements are reliable because primary colonies divided in half formed two groups of secondary colonies (on two separate plates) that had indistinguishable mean colony sizes. Based on these observations, a divided-colony procedure was devised to detect the drug response of heterogeneous cell populations. Primary colonies are divided into two groups of cells, one of which is treated with a drug and the other is left untreated as a control. The size distribution of treated secondary colonies is then compared to that of the untreated control and to that of the primary colony from which it was derived. The divided-colony procedure is proposed as a modification of the human-tumor-colony system to increase the sensitivity and reliability of in vitro procedures used to determine the drug response of heterogeneous tumor-cell populations.