Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.
Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.
复制标题
单一乳腺肿瘤的肿瘤细胞亚群之间药物敏感性的异质性。
作者：
G. Heppner;D. Dexter;T. DeNucci;F. Miller;P. Calabresi
体内测试了源自单亲株 BALB/cfC3H 乳腺癌的三个不同肿瘤细胞亚群对环磷酰胺、甲氨蝶呤和 5-氟尿嘧啶的敏感性。皮下注射后 2 天开始治疗。肿瘤细胞注射或当肿瘤变得可触及时。每周给予一次，持续 4 周。观察小鼠原发植入物的生长和自发转移的发展。这三个亚群对药物的敏感性存在显着差异。药物的作用范围从诱导“原发灶”消退到增强转移灶。对原发生长的影响独立于对转移的影响。不同亚人群中给药时间的影响也不同。还用甲氨蝶呤和5-氟尿嘧啶对这些亚系进行了体外测试。同样，药物抑制细胞分裂的敏感性存在显着差异。体外的相对敏感性与体内观察结果不相关。单一肿瘤内存在对治疗剂敏感性不同的肿瘤细胞亚群，这对开发能够预测药物反应的测定方法和选择联合疗法提出了挑战。
Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.