Tumor heterogeneity and stability of the metastatic phenotype of mouse KHT sarcoma cells.
Tumor heterogeneity and stability of the metastatic phenotype of mouse KHT sarcoma cells.
复制标题
小鼠 KHT 肉瘤细胞的肿瘤异质性和转移表型的稳定性。
作者：
A. Chambers;R. Hill;V. Ling
转移能力的异质性已在许多不同肿瘤的体外克隆细胞系的模型系统中得到证实。我们研究了小鼠KHT肉瘤细胞的克隆多样性，无论是体外克隆还是体内克隆，通过确定它们在静脉注射到同基因小鼠后形成肺菌落的能力。在体外和体内分离的克隆中都发现了广泛的转移能力，这表明所观察到的多样性不是由于在体外生长过程中发生的任何选择。四个体外分离克隆，两个高转移能力和两个低转移能力，然后在体外生长3至4个月的时间内研究了稳定性。高转移细胞的表型保持相对稳定，随着时间的推移仅略有下降。然而，具有低转移能力的克隆在培养的前30天内形成肺菌落的能力显着增加，然后稳定在比原始值高约10倍的水平。然而，即使在这种增加之后，高对和低对克隆的转移能力仍然存在大约10倍的差异。细胞悬浮液注入塑料微球后，四种细胞系形成的肺菌落数量均显著增加。低转移能力的细胞受到微球的影响更大，导致培养30天后四个克隆之间的差异消除。这一结果表明，使用微球可以提供一种方法来区分影响细胞形成肺转移能力的不同细胞特性。
Heterogeneity in metastatic ability has been demonstrated in model systems for in vitro-cloned cell lines for a number of different tumors. We have examined the clonal diversity of mouse KHT sarcoma cells cloned either in vitro or in vivo by determining their ability to form lung colonies following i.v. injection into syngeneic mice. A wide range of metastatic ability was found in both the in vitro- and in vivo-isolated clones, suggesting that the diversity observed is not due to any selection occurring during in vitro growth. The stability of four in vitro-isolated clones, two of high metastatic and two of low metastatic ability, was then studied over a period of 3 to 4 months of growth in vitro. The phenotype of the highly metastatic cells remained relatively stable, declining only slightly over time. The clones with low metastatic ability, however, demonstrated a significant increase in ability to form lung colonies over the first 30 days in culture before becoming stable at levels approximately 10-fold higher than their original values. Even after this increase, however, there remained a difference of about a factor of 10 in the metastatic ability of the high and low pairs of clones. It was found that the number of lung colonies formed by all four cell lines was significantly increased when plastic microspheres were injected with the cell suspension. The cells with low metastatic ability were affected to a greater degree by the microspheres, resulting in the elimination of the difference between the four clones after 30 days in culture. This result suggests that the use of microspheres may provide a means to distinguish different cellular properties which affect the ability of cells to form lung metastases.