Kath R, Jambrosic J A, Holland L, Rodeck U, Herlyn M
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Cancer Res. 1991 Apr 15;51(8):2205-11.
Growth autonomy and high levels of invasiveness are characteristics of human melanoma cells that are metastatic in vivo. By consecutive passage through a reconstructed basement membrane, we have selected from 5 of 6 primary melanoma cell lines variants which show an up to 10-fold increase in invasiveness. The invasive variants grew more rapidly than the parental, noninvasive cells in serum- and growth factor-free medium and one of the 3 variant cell lines with the highest invasive capacity in vitro metastasized to the lungs when injected s.c. into nude mice. In a second approach, variants of 6 primary melanoma cell lines were clonally selected in medium without exogenous growth factors (protein-free medium). These selected cells showed higher invasive properties in vitro and in vivo than the parental cells. Clones of invasive and growth factor-independent cell variants were heterogenous and changed over time in the absence of selected pressure to a phenotype similar to that of parental nonselected cells. These results indicate that primary melanoma cells contain subpopulations of cells that have the phenotype of an advanced (metastatic) stage of tumor progression, but this phenotype is not stable without selective pressure.
生长自主性和高度侵袭性是在体内具有转移能力的人类黑色素瘤细胞的特征。通过连续传代培养穿过重建的基底膜，我们从6个原发性黑色素瘤细胞系中的5个中筛选出了侵袭性提高了10倍的变体。在无血清和生长因子的培养基中，侵袭性变体比亲代非侵袭性细胞生长得更快，并且在体外具有最高侵袭能力的3个变体细胞系之一，经皮下注射到裸鼠体内后转移至肺部。在第二种方法中，在无外源性生长因子的培养基（无蛋白培养基）中对6个原发性黑色素瘤细胞系的变体进行克隆筛选。这些筛选出的细胞在体外和体内均表现出比亲代细胞更高的侵袭特性。侵袭性和生长因子非依赖性细胞变体的克隆是异质性的，并且在没有选择压力的情况下，随着时间的推移会转变为与亲代未选择细胞相似的表型。这些结果表明，原发性黑色素瘤细胞包含具有肿瘤进展晚期（转移）阶段表型的细胞亚群，但在没有选择压力的情况下，这种表型并不稳定。
