Laboratory of Pathology, School of Medicine, University of Pennsylvania, Philadelphia.
J Exp Med. 1939 Aug 31;70(3):257-68. doi: 10.1084/jem.70.3.257.
The adenocarcinoma which commonly occurs in the kidney of leopard frogs has been transplanted into the anterior chamber of the eye where its growth characteristics have been studied by direct observation with the slit-lamp microscope. Such observations have been amplified by photographs taken at intervals to furnish permanent and objective records of the mode of development and progress of the growths, from earliest to advanced stages. The fifteen tumors which fumished the transplants were typical large invasive adenocarcinomas having the usual irregular and apparently anarchic arrangement of their component tubules and acini. However, the transplanted tumors developed according to definite and well defined structural patterns, their type depending on the immediate physical environment. Three such morphogenetic patterns were observed. Unimpeded outgrowths into the aqueous tumor characteristically assumed a tubulo-papillary arrangement; the earliest formation consisted of solid, purely epithelial cylinders, many of which at later stages acquired a lumen and thus became tubular; generally only the coarser projections developed vascular stalks. Further growth was made by repeated branching, and lateral outpouching of the tubules. Where the tumor grew in contact with firm, even surfaces, such as lens or cornea, differentiation was lost and broad membranes formed which gradually spread over the surfaces; secondarily, new cylindrical or tubular processes arose from such indifferent cellular carpets. Where the tumor made contact with loose tissue such as iris, it invaded this organ, and, supported by the stroma, assumed an acinar pattern quite like that of the original adenocarcinoma of the kidney. All three types of growth were sometimes found coexisting in different portions of the anterior chamber. The rate of growth of transplanted tumors was followed by photographic records taken periodically. A fairly constant mode of progress was noted: after a variable period of lag and a period of gradual outgrowth, there followed rather abruptly a short period of rapid growth, after which growth increments gradually became smaller. Variations in growth rate due to season and to temperature were evident, but further experiments are required to evaluate the part played by these factors. Attempts to transplant normal kidney in the anterior chamber were unsuccessful. The manner of growth in the vitreus was found to be similar to that in the anterior chamber. The factors that determine the manner of tumor growth are as yet imperfectly understood. Evidence is however accumulating to the effect that neoplastic growth is not as anarchic as is suggested by histologic sections of some tumors (26). The present experiments support the view that cancers are much more responsive to the laws governing growth and organization than is generally supposed.
通常发生在豹蛙肾脏中的腺癌已被移植到眼前房,在那里可以通过裂隙灯显微镜进行直接观察来研究其生长特征。通过定期拍摄照片来放大这些观察结果,为肿瘤的生长和进展模式提供永久性和客观的记录,从最早到晚期阶段。提供移植的十五个肿瘤是典型的大型侵袭性腺癌,其组成小管和腺泡的排列通常不规则且明显杂乱无章。然而,移植的肿瘤按照明确的结构模式发展,其类型取决于直接的物理环境。观察到三种形态发生模式。无阻地生长到眼水中的肿瘤通常呈管状乳头状排列;最早的形成由实心的、纯粹的上皮圆柱体组成,其中许多在后期获得管腔并因此成为管状;通常只有较粗的突起形成血管茎。进一步的生长是通过反复分支和管状的侧向膨出实现的。当肿瘤在与坚硬、平整的表面(如晶状体或角膜)接触时,会失去分化并形成宽阔的膜,这些膜逐渐覆盖在表面上;其次,新的圆柱形或管状突起从这种无关紧要的细胞地毯上出现。当肿瘤与疏松的组织(如虹膜)接触时,它会侵入该器官,并在基质的支撑下,呈现出与肾脏原始腺癌非常相似的腺泡模式。所有三种类型的生长都可以在眼前房的不同部位同时发现。通过定期拍摄的照片记录来跟踪移植肿瘤的生长速度。注意到一种相当恒定的进展模式:在一个可变的潜伏期和一个逐渐生长的阶段之后,紧接着是一个短暂的快速生长阶段,之后生长增量逐渐变小。由于季节和温度的变化导致的生长速度变化是明显的,但需要进一步的实验来评估这些因素所起的作用。在前房移植正常肾脏的尝试均未成功。在玻璃体内的生长方式与在前房内的生长方式相似。决定肿瘤生长方式的因素尚未完全理解。然而,有证据表明,肿瘤的生长并不像某些肿瘤的组织学切片所表明的那样杂乱无章(26)。目前的实验支持这样的观点,即癌症对控制生长和组织的规律的反应比人们通常认为的要敏感得多。