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.

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Supported in parts by Grants-in-Aid for Cancer Research 50-14 from the Ministry of Health and Welfare and 101062 from the Ministry of Education, Science and Culture, Japan. This is Paper 9 of a series on the establishment of transplantable human cancers in nude mice and their application to basic and clinical cancer research.

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