Histologic Analyses of Experimental Tumors From Mouse Blastocyst-Derived Cell Lines

Abstract

Previous work has shown that established cell lines can be derived from cultured mouse blastocysts. Although these cell lines differed from one another morphologically, immunologically, and biochemically, it has not been easy to determine what embryonic cell type (if any) each cell line represents. We showed in this report that these blastocyst-derived lines could produce tumors in syngeneic mice at low yields and presented the results of histologic analyses of the tumors which we carried out to learn more about the kinds of cells present in each of the lines. Tumors derived from cell line MB2 contained two kinds of cells. Most of the cells were similar to those found in so-called “parietal yolk sac carcinomas,” secreted Reichert's membrane-like material, and could be found in subsequent transplant generations. The other cell type resembled trophoblast giant cells morphologically and did not survive transplantation. These results showed that MB2 contained cells which were either parietal endoderm cells or a closely related precursor. The tumor derived from MB4 consisted of small, closely packed cells intermixed with larger cells with foamy cytoplasm and occasional giant cells. Cells in subsequent passages of the tumor were often organized into acinar clusters. Biochemical evidence has suggested that MB4 cells resembled one or both components of visceral yolk sac. Visceral yolk sac sarcomas have not previously been reported; the MB4derived tumor may prove to be the first. Tumors derived from line MB31 contained both fibroblastic and epithelioid cell types which could not be more definitively identified. Cultures derived from each kind of tumor in each case contained cells morphologically characteristic of those in the originally inoculated population. Our results showed that tumors produced from blastocyst-derived cell lines did not resemble the teratocarcinomas which formed when blastocysts were implanted into an ectopic site in vivo: They did not contain a wide variety of cell types, nor did they possess pluripotent embryonal carcinoma “stem” cells characteristic of the teratocarcinoma. That each blastocyst-derived line gave rise to a different kind of tumor suggested that each line may have been made up of cells “trapped” at some stage characteristic of the development of a particular embryonic or extraembryonic tissue. However, each tumor did contain at least two distinct cell types; this suggested that cells in the blastocyst-derived lines, though restricted in their developmental potential, may not yet have been completely determined.