Gerharz C D, Bracke M E, Mareel M M, Gabbert H E
Department of Pathology, Heinrich Heine University of Düsseldorf, Germany.
Clin Exp Metastasis. 1993 Jan;11(1):55-67. doi: 10.1007/BF00880066.
Three clonal subpopulations (A, B, C) isolated from the same rhabdomyosarcoma of the rat and differing in their degree of spontaneous differentiation were tested for their invasive potential before and after differentiation induction with retinoic acid (RA), N-monomethylformamide (NMF) and sodium butyrate (NaBut). Invasive potential was analysed in an in vitro assay using embryonic chick heart fragments in organotypic culture. In standard culture medium, all three subpopulations were shown to be invasive, progressively replacing the chick heart fragments within 7-11 days after confrontation. After exposure to RA, NMF or NaBut, marked differences in the invasive potential of these subpopulations were, however, observed. Subpopulation C exhibited a pronounced decline in invasive potential, as evidenced by a significant decrease (P = 0.005) in the proportion of chick heart fragments with advanced stages of invasion. This response, however, was confined to the differentiation-inducing agents RA and NaBut, which had also produced a marked increase in morphological and/or biochemical differentiation (P = 0.0001). In contrast, NMF, which had only minor effects on differentiation, failed to affect the invasive potential of subpopulation C. In subpopulation B, a transient inhibition of single cell invasion became evident after exposure to RA, whereas NMF and NaBut failed to affect the invasive potential in spite of minor effects on differentiation. In the least differentiated subpopulation A, which was shown to be refractory to the differentiation-inducing effects of RA, NMF and NaBut, there was also no observation of any reduction of invasive potential. The results of our study demonstrate that differentiation-inducing agents can significantly reduce the invasive potential of malignant tumors, although marked differences of response are to be expected between the different subpopulations of a tumor.
从大鼠同一横纹肌肉瘤中分离出三个克隆亚群（A、B、C），它们的自发分化程度不同，在用视黄酸（RA）、N-单甲基甲酰胺（NMF）和丁酸钠（NaBut）诱导分化前后，检测了它们的侵袭潜能。在体外实验中，使用器官型培养的鸡胚心脏片段分析侵袭潜能。在标准培养基中，所有三个亚群都显示出具有侵袭性，在接触后7-11天内逐渐取代鸡胚心脏片段。然而，在暴露于RA、NMF或NaBut后，观察到这些亚群在侵袭潜能上存在显著差异。亚群C的侵袭潜能明显下降，侵袭晚期的鸡胚心脏片段比例显著降低（P = 0.005）证明了这一点。然而，这种反应仅限于诱导分化的试剂RA和NaBut，它们也使形态和/或生化分化显著增加（P = 0.0001）。相比之下，对分化只有轻微影响的NMF未能影响亚群C的侵袭潜能。在亚群B中，暴露于RA后，单细胞侵袭出现短暂抑制，而NMF和NaBut尽管对分化有轻微影响，但未能影响侵袭潜能。在分化程度最低的亚群A中，已证明其对RA、NMF和NaBut的诱导分化作用不敏感，也未观察到侵袭潜能有任何降低。我们的研究结果表明，诱导分化剂可以显著降低恶性肿瘤的侵袭潜能，尽管肿瘤的不同亚群之间预期会有明显的反应差异。
