Chemically induced differentiation of murine embryonal carcinoma in vivo: transplantation of differentiated tumors

Murine embryonal carcinoma tumors were induced to differentiate in vivo by administration of retinoic acid. Six long-term surviving animals had seven slowly growing tumors which were transplanted s.c. into strain 129 mice. Untreated embryonal carcinomas were transplanted as controls. All of the 16 control transplants grew rapidly and killed their hosts within 25 days. All of the 24 transplants of retinoic acid-differentiated tumor survived. Sixteen experimental transplants originating from five original tumors showed no or slow growth for up to 16 weeks and were found to be histologically benign cystic teratomas. Two original tumors gave rise to eight relatively rapidly growing transplants. One tumor resulted in four histologically similar solid tumors which resembled chondrosarcomas, and the second tumor gave rise to four histologically similar solid tumors which proved to be a mixture of glioma and chondrosarcoma. Examination of the tumor sources of these latter transplants showed benign cystic teratomas with focal solid, mitotically active cellular areas which were histologically similar to the transplants. These data confirm that retinoic acid-induced differentiation of murine embryonal carcinoma cells results in altered biological potential of these cells and usually the formation of a benign teratoma. Rarely (about 1 per 2 X 10(8], the resulting differentiated cells will give rise to rapidly growing, histologically malignant tumors. One can predict such biological propensity when solid, mitotically active areas in the original tumor are found.