Poste G, Doll J, Brown A E, Tzeng J, Zeidman I
Cancer Res. 1982 Jul;42(7):2770-8.
Tumors produced by s.c. injection of uncloned B16 melanoma cell lines contain clonal tumor cell subpopulations with widely differing metastatic properties, including clones that are nonmetastatic. Similar metastatic heterogeneity exists in clones isolated from the same cell lines cultured in vitro. In B16 melanoma sublines (B16-BL6, B16-BV8, and B16-BP8) selected for enhanced invasive and metastatic behavior, the proportion of clones with high metastatic capacity is increased relative to the parent cell line. The cellular composition of metastases produced by s.c. or i.v. injection of the uncloned parent cell line has also been examined. Some metastases are populated by clones with indistinguishable metastatic properties (intralesional clonal homogeneity) while others yield clones with different metastatic properties (intralesional clonal heterogeneity). The range of clonal diversity in heterogeneous metastases is, however, substantially less than in the parent line. The number of metastases yielding clones with heterogeneous metastatic phenotypes is higher for "spontaneous" metastases arising from s.c. tumors than in "experimental" metastases produced by i.v. injection of single-cell suspensions. Studies using B16 cells bearing specific biochemical markers indicate that clonally homogeneous metastases are of monoclonal origin and that metastases populated by clones with heterogeneous metastatic phenotypes are of polyclonal origin.
通过皮下注射未克隆的B16黑色素瘤细胞系产生的肿瘤含有具有广泛不同转移特性的克隆肿瘤细胞亚群，包括非转移性克隆。从体外培养的相同细胞系中分离出的克隆中也存在类似的转移异质性。在选择用于增强侵袭和转移行为的B16黑色素瘤亚系（B16-BL6、B16-BV8和B16-BP8）中，具有高转移能力的克隆比例相对于亲本细胞系有所增加。还检查了通过皮下或静脉注射未克隆的亲本细胞系产生的转移灶的细胞组成。一些转移灶由具有难以区分的转移特性的克隆组成（病灶内克隆同质性），而其他转移灶则产生具有不同转移特性的克隆（病灶内克隆异质性）。然而，异质性转移灶中克隆多样性的范围明显小于亲本系。皮下肿瘤产生的“自发”转移灶中产生具有异质转移表型克隆的转移灶数量高于静脉注射单细胞悬液产生的“实验性”转移灶。使用带有特定生化标记的B16细胞进行的研究表明，克隆同质转移灶起源于单克隆，而异质转移表型克隆组成的转移灶起源于多克隆。
