Hyperglycosylated hCG in gestational implantation and in choriocarcinoma and testicular germ cell malignancy tumorigenesis

OBJECTIVE: Hyperglycosylated human chorionic gonadotropin (hCG-H) is a carbohydrate variant of hCG with double-sized oligosaccharide side chains. While hCG-H is produced exclusively by stem cytotrophoblast cells in gestational choriocarcinoma, by pregnancy cytotrophoblast at implantation and by the cytotrophoblast produced in testicular malignancies, regular hCG is produced only by differentiated syncytiotrophoblast cells. STUDY DESIGN: hCG-H was measured using the Nichols Advantage hCG-H assay (Nichols Institute Diagnostics, San Clemente, California). RESULTS: hCG-H has a function separate from regular hCG. hCG-H, but not regular hCG, acts in vivo and in vitro to promote invasion, whether invasion through membranes or tumor formation. Invasion or tumorigenesis is completely blocked by administration of specific antibody to hCG-H. The same hCG-H-modulated invasion mechanisms are observed in early pregnancy, gestational choriocarcinoma and testicular cancers. CONCLUSION: hCG-H is a cytokinelike molecule, produced by cells different from those that make regular hCG and having a completely separate function. It appears to be the modulator of invasion as in implantation of pregnancy, gestational choriocarcinoma and testicular cancer malignancy.