Stackpole C W, Alterman A L, Valle E F
Department of Pathology, New York Medical College, Valhalla 10595.
Clin Exp Metastasis. 1991 May-Jun;9(3):319-32. doi: 10.1007/BF01753733.
Metastatic clones of the mouse B16 melanoma spontaneously disseminate from subcutaneous tumors throughout the body in two stages, initially to the lungs and secondarily from established lung metastases to systemic sites. From the heterogeneous 'parent' B16 melanoma cell line and from two representative clones, G3.5 and G3.12, cell populations were selected after one or more cycles of tumor growth or metastasis to a particular site, to determine whether metastatic variants with greater organ preference or specificity could be generated. Variants with enhanced secondary metastatic activity were obtained only from G3.12 tumor-disseminated metastases growing in the lungs or in systemic organs. Regardless of the organ of selection or the number of selection cycles, all variants exhibited an overall increase in secondary metastasis incidence and burden in the brain, adrenals, kidneys and ovaries, but no organ preference or specificity was obtained. Populations that grew especially well in the brain, ovaries or liver following intravascular injection were either non-metastatic or exhibited no organ preference during spontaneous metastasis. The increased secondary metastatic activity of G3.12 variants was apparently not due to either longer host survival or to tumor-disseminated cells bypassing the lungs, but may result from enhanced growth potential or greater secondary dissemination capability imparted during growth as lung metastases.
小鼠B16黑色素瘤的转移克隆会从皮下肿瘤自发地扩散至全身，分两个阶段进行，最初转移至肺部，其次从已形成的肺转移灶扩散至全身其他部位。从异质性的“亲本”B16黑色素瘤细胞系以及两个代表性克隆G3.5和G3.12中，在肿瘤生长或转移至特定部位一个或多个周期后选择细胞群体，以确定是否能产生具有更强器官偏好性或特异性的转移变体。仅从在肺部或全身器官中生长的G3.12肿瘤播散性转移灶中获得了具有增强的二次转移活性的变体。无论选择的器官或选择周期的数量如何，所有变体在脑、肾上腺、肾脏和卵巢中的二次转移发生率和负担均呈现总体增加，但未获得器官偏好性或特异性。血管内注射后在脑、卵巢或肝脏中生长特别良好的细胞群体要么不具有转移性，要么在自发转移过程中未表现出器官偏好性。G3.12变体增强的二次转移活性显然不是由于宿主存活时间延长或肿瘤播散细胞绕过肺部所致，而是可能源于作为肺转移灶生长期间赋予的生长潜力增强或二次播散能力增强。
