Valle E F, Zalka A D, Groszek L, Stackpole C W
Department of Experimental Pathology, New York Medical College, Valhalla 10595.
Clin Exp Metastasis. 1992 Nov;10(6):419-29. doi: 10.1007/BF00133471.
The mouse B16 melanoma metastasizes first to the lungs and secondarily to systemic sites, involving mainly the adrenals, ovaries and pancreas. Systemic colonization effected by intracardiac injection of tumor cells establishes similar patterning, but in addition frequently colonizes the bones. To assess possible systemic site influences on metastasis and colony formation, the capacity of B16 melanoma cells to proliferate in these sites in vivo and in ex vivo explants following intracardiac injection was examined. Effects of cells isolated from these sites, and of organ- or tissue-conditioned medium, on growth of B16 cells in monolayer culture were also studied. Injected fluorochrome-labeled tumor cells initially distributed without site preference, but within 48 h had begun proliferating in the adrenals, ovaries and lungs, while remaining static in the pancreas and bones, and disappearing from the spleen, liver, kidneys, brain, and skeletal muscles. Mitogenic activity releasable in soluble form was associated with all favorable organs and tissues and was the predominant influence of those tissues on cultured tumor cells. In contrast, the overall effects of liver, spleen, kidney, and brain tissues were to inhibit tumor cell growth. Soluble growth-promoting activity enhanced clonogenic growth of isolated tumor cells stimulated by mouse serum, suggesting that metastasis or colony formation might be stimulated in favorable sites by those factors together with blood-borne growth factors. The observed effects of organ- and tissue-derived cells and soluble factors on tumor cells generally reflected the in vivo consequences of tumor cell entrapment in the corresponding sites. However, the failure of metastases to develop in the bones, which are favorable sites for colonization by the same cells, remains puzzling.
小鼠B16黑色素瘤首先转移至肺部，其次转移至全身其他部位，主要累及肾上腺、卵巢和胰腺。通过心内注射肿瘤细胞实现的全身定植呈现出类似的模式，但除此之外，还经常定植于骨骼。为了评估全身其他部位对转移和集落形成的可能影响，研究了心内注射后B16黑色素瘤细胞在这些部位体内及体外植块中增殖的能力。还研究了从这些部位分离的细胞以及器官或组织条件培养基对单层培养的B16细胞生长的影响。注射荧光染料标记的肿瘤细胞最初无部位偏好地分布，但在48小时内开始在肾上腺、卵巢和肺中增殖，而在胰腺和骨骼中保持静止，并从脾脏、肝脏、肾脏、脑和骨骼肌中消失。以可溶形式释放的促有丝分裂活性与所有有利的器官和组织相关，并且是这些组织对培养的肿瘤细胞的主要影响。相比之下，肝脏、脾脏、肾脏和脑组织的总体作用是抑制肿瘤细胞生长。可溶性生长促进活性增强了小鼠血清刺激的分离肿瘤细胞的克隆生长，这表明在有利部位，这些因子与血源性生长因子一起可能刺激转移或集落形成。观察到的器官和组织来源的细胞及可溶性因子对肿瘤细胞的影响通常反映了肿瘤细胞在相应部位滞留的体内后果。然而，骨骼是相同细胞定植的有利部位，但转移却未能在骨骼中发生，这仍然令人费解。
