University of Leuven, Rega Institute for Medical Research, Belgium.
Externalization of the visceral yolk sac, after fetectomy, induces the development of extra-embryonal fetal tumors in rodents. These tumors are either benign teratomas that appear 3 to 4 weeks after the displacement of the yolk sac or malignant tumors, i.e. yolk sac carcinomas. The latter appear 4 to 8 months after the surgery. If however, Mouse Sarcoma Virus (MSV) is injected in the placentas at the time of fetectomy (day 12 of pregnancy) the malignant tumors develop much earlier (2 to 3 months after surgery) and some display characteristics of embryonal carcinoma. Whether virus induced or not, the yolk sac carcinomas that develop from the displaced visceral yolk sac possess the same morphological and biological characteristics. They are composed of both parietal and visceral yolk sac structures and sometimes trophoblast. The tumors metastasize, grow in ascites form and kill their host. They are readily transplantable in syngeneic rats and grow in tissue culture as an epithelial-like sheet of cells. On the other hand, the benign teratomas are composed of various well differentiated adult tissues. In these tissues, derivatives of all three germ layers are observed. Numerous experiments prove that the stem cells for these various adult tissues are not germ cells. Instead the stem cells are multipotential cells that arise in the displaced yolk sac by a process of dedifferentiation. These poorly differentiated cells originate from the endoderm of the displaced visceral yolk sac. By redifferentiation they give rise to the various adult tissues characteristic for benign teratomas. The multipotential poorly differentiated cells are also likely to be the target cells for malignant transformation. Malignant transformation of these cells, whether induced by a virus or spontaneously occurring in the displaced yolk sac, leads not only to the development of yolk sac carcinomas and eventually embryonal carcinoma but also, although rarely, to choriocarcinoma. The latter tumor is transplantable in allogeneic hosts. It is hormonally active since it secretes lactogen and progesterone. The extra-embryonal fetal tumors and in particular the rat yolk sac carcinomas and choriocarcinoma proved to be a good source for the detection of oncofetal antigens. At least two different oncofetal endodermal antigens were detected with monoclonal antibodies (mab) made after immunization with yolk sac carcinoma. Another mab, made against choriocarcinoma, was found to react specifically with the cytotrophoblast both in the normal placenta and in the tumor. No other placental cells showed a positive reaction.