Production of alpha-fetoprotein and normal serum proteins by xenotransplanted human hepatomas in relation to their growth and morphology.
Production of alpha-fetoprotein and normal serum proteins by xenotransplanted human hepatomas in relation to their growth and morphology.
复制标题
异种移植的人肝癌产生的甲胎蛋白和正常血清蛋白与其生长和形态有关。
作者：
S. Hirohashi;Y. Shimosato;T. Kameya;T. Koide;T. Mukojima;Y. Taguchi;K. Kageyama
19例人肝细胞癌中有5例和5例肝母细胞瘤中有2例可连续移植于裸鼠（BALB/c，nu/nu）。五个肝细胞癌中有四个保留了原始组织学，并显示了肝细胞的一些超微结构特征，尽管它们往往失去与窦状血管的密切联系，其中一个含有一些腺结构。根据组织切片上的细胞质数量和与正常肝细胞的超微结构相似性，将其分为高分化（Li-19）、中等分化（Li-23）和中等分化（Li-7和Li-16）肝细胞癌。所有这四个肿瘤产生甲胎蛋白和正常血清蛋白。甲胎蛋白和白蛋白的产生量与生长速度和形态分化程度成正相关或负相关。快速生长、低分化的肿瘤比缓慢生长、高分化的肿瘤产生更多的甲胎蛋白和白蛋白。其中一株（Li-4）来源于小梁状肝细胞癌，失去了肝细胞的形态特征，变成了低分化腺癌，并且不产生可检测量的甲胎蛋白或正常血清蛋白。
可移植性肝母细胞瘤（Li-15和Li-24）由肿瘤上皮细胞组成，其超微结构类似于胎肝细胞;在连续转移过程中，基质成分、类骨质和髓外造血灶丢失。它们大量产生甲胎蛋白和正常血清蛋白。
这些结果表明生长速率、向肝细胞的细胞学分化和产生甲胎蛋白的能力之间呈正相关，这可以通过肝细胞癌的分化可能对应于胎肝成熟的假设来解释。然而，低分化肿瘤白蛋白的产生增加与这一假设相矛盾，并表明肿瘤性肝细胞中蛋白质合成的调节存在一些缺陷。
Five of 19 human liver cell carcinomas and two of five hepatoblastomas could be serially transplanted in nude mice (BALB/c, nu/nu). Four of five liver cell carcinomas retained the original histology and revealed some ultrastructural features of liver cells, although they tended to lose intimate association with sinusoidal vessels and one of them contained some glandular structures. They were divided into well-differentiated (Li-19), moderately well-differentiated (Li-23), and moderately differentiated (Li-7 and Li-16) liver cell carcinomas by the amount of cytoplasm on tissue sections and by ultrastructural similarity to normal liver cells. All of these four tumors produced both α-fetoprotein and normal serum proteins. Amounts of α-fetoprotein and albumin produced were related to growth rates and the degree of morphological differentiation directly or inversely. The rapidly growing, less-differentiated tumor produced much larger amounts of α-fetoprotein and albumin than did the slowly growing, better-differentiated tumor. One of the strains (Li-4), which derived from a trabecular liver cell carcinoma, lost the morphological features of liver cells, became a poorly differentiated adenocarcinoma, and did not produce detectable amounts of either α-fetoprotein or normal serum proteins.
Transplantable hepatoblastomas (Li-15 and Li-24) consisted of neoplastic epithelial cells, which ultrastructurally resembled fetal liver cells; and the stromal component, osteoids, and foci of extramedullary hematopoiesis were lost during serial transfers. They produced α-fetoprotein and normal serum proteins in quantity.
These results suggest positive correlation among growth rates, cytological differentiation toward liver cells, and the ability to produce α-fetoprotein, which could be explained by the assumption that the differentiation of liver cell carcinomas might correspond to the maturation of the fetal liver. However, the increased production of albumin by less differentiated tumors contradicts the assumption and suggests some defects in regulation of protein synthesis in neoplastic liver cells.