Fate of embryonal carcinoma cells injected into postimplantation mouse embryos.
Embryonal carcinoma (EC) cells, stem cells of teratocarcinoma, represent an excellent model to study the developmental mechanisms that, inappropriately reactivated, can drive tumorigenesis. EC cells are very aggressive, and grow rapidly when injected into adult syngeneic mice. However, when injected into blastocysts, they revert to normality, giving rise to chimeric animals. In order to study the ability of postimplantation embryonic environment to "normalize" tumorigenic cells, and to study their homing, we transplanted F9, Nulli-SCC1, and P19 EC cells into 8 to 15-day allogenic CD1 mouse embryos, into allogenic CD1 newborns, and into syngeneic adult mice, and evaluated tumor formation, spreading, and homing. We found that, although at all embryonic stages successful transplantation occurred, the chances of developing tumors after birth increased with the time of injection of EC cells into the embryo. In addition, using enhanced green fluorescent protein-expressing F9 cells, we demonstrated that the cells not giving rise to tumors remained latent and could be tracked down in tissues during adulthood. Our data indicate that the embryonic environment retains a certain ability to "normalize" tumor cells also during post-implantation development. This could occur through yet unknown epigenetic signals triggering EC cells' differentiation.
Astigiano
Simonetta
S
S.S. Animali Transgenici, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy. Simonetta.Astigiano@istge.it
Damonte
Patrizia
P
Fossati
Sara
S
Boni
Luca
L
Barbieri
Ottavia
O
D000367:Age Factors; D000818:Animals; D002460:Cell Line; D033041:Embryo Research; D054278:Embryonal Carcinoma Stem Cells; D047108:Embryonic Development; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000637:transplantation*; D011247:Pregnancy; D018243:Teratocarcinoma / Q000737:chemistry / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins