Stackpole C W, Fornabaio D M, Alterman A L
Int J Cancer. 1985 May 15;35(5):667-74. doi: 10.1002/ijc.2910350516.
Three distinct dissemination-related phenotypes have been recognized in clones of the mouse B16 melanoma based on in vivo behavior: metastatic (spontaneously disseminating to the lungs from solid tumors), colonizing (capable of forming tumor colonies in the lungs following intravenous injection), and null (tumorigenic but non-metastatic and non-colonizing). From a progenitor null clone, G3, subclones that became phenotypically diversified in vitro (metastatic G3.5 and null G3.15) and in vivo (metastatic G3.12 and colonizing G3.26) were derived. During long-term culturing, G3 cells became metastatic and then lost that activity, G3.5 and G3.12 cells gradually lost metastatic activity, and G3.26 cells became slightly metastatic and non-colonizing. Subclone G3.15 became highly metastatic after a single subcutaneous (s.c.) tumor passage. In aged mice, and in young mice injected with incompletely-tumorigenic cell doses, G3 and G3.26 s.c. tumors were metastatic, but cells cultured from those tumors or metastases were non-metastatic when tested in young mice at standard highly-tumorigenic cell doses. The behavior of G3.5 and G3.12 tumors was not altered in aged mice or when tumors were initiated with small cell inocula. Analysis of growth characteristics associated with these phenotypic interconversions indicated that lung-colonizing potential was directly related to the ability of the cells to grow as multicell colonies in 0.3% agar, and that metastatic activity was expressed by tumors that grew at moderate rates. In young mice receiving standard cell doses, G3.5 and G3.12 tumors inherently grew at that rate, whereas G3 and G3.26 tumors grew more rapidly and G3.15 tumors grew more slowly. Regardless of inherent phenotype, all clones were capable of expressing metastatic activity, at least transiently, as tumor growth was altered to moderate rates. Expression of metastatic behavior might, therefore, be regulated to some extent by tumor growth characteristics.
基于体内行为，在小鼠B16黑色素瘤克隆中已识别出三种与播散相关的不同表型：转移型（从实体瘤自发播散至肺部）、定植型（静脉注射后能够在肺部形成肿瘤集落）和无转移型（具有致瘤性但不转移也不定植）。从祖代无转移型克隆G3衍生出了在体外（转移型G3.5和无转移型G3.15）和体内（转移型G3.12和定植型G3.26）表型多样化的亚克隆。在长期培养过程中，G3细胞变得具有转移性，随后失去该活性，G3.5和G3.12细胞逐渐丧失转移活性，而G3.26细胞变得稍有转移性且不定植。亚克隆G3.15在单次皮下肿瘤传代后变得高度转移。在老年小鼠以及注射不完全致瘤细胞剂量的年轻小鼠中，G3和G3.26皮下肿瘤具有转移性，但当以标准高致瘤细胞剂量在年轻小鼠中进行测试时，从这些肿瘤或转移灶培养的细胞无转移性。G3.5和G3.12肿瘤在老年小鼠中的行为未改变，或者当用小细胞接种启动肿瘤时也未改变。对与这些表型相互转化相关的生长特性分析表明，肺部定植潜能与细胞在0.3%琼脂中形成多细胞集落生长的能力直接相关，并且转移活性由以中等速率生长的肿瘤表现出来。在接受标准细胞剂量的年轻小鼠中，G3.5和G3.12肿瘤固有地以该速率生长，而G3和G3.26肿瘤生长更快，G3.15肿瘤生长更慢。无论固有表型如何，所有克隆都能够表达转移活性，至少是短暂表达，因为肿瘤生长改变为中等速率。因此，转移行为的表达可能在一定程度上受肿瘤生长特性调节。
