IGF-II-like immunoreactivity in human tissues, neuroendocrine tumors, and PC12 cells.

We looked for cells that reacted with monoclonal antibodies against rat insulin-like growth factor II (IGF-II). We found them in human fetal kidneys in the 14th week of gestation and in adult adrenal medullas but not in human liver, pancreas, pituitary gland, or thymus. Every pheochromocytoma in a group of 20 had IGF-II-like immunoreactive cells, as did three out of four ganglioneuroblastomas (one of which was heterotransplantable in athymic nude mice) and one carotid body tumor. Using the electron microscope we localized the immunoreactivity in pheochromocytoma cells to their neurosecretory granules of the non-catecholamine type. We failed to find any IGF-II-reactive cells among the pancreatic islet cell tumors, neuroblastomas, medullary carcinomas of the thyroid, retinoblastomas, and Wilms' tumor we studied. One line of human neuroblastoma cells did show some immunoreactivity after treatment with dbcAMP. Additionally, the rat pheochromocytoma cell line PC12 and its subline PC12h occasionally produced a few immunostained cells. These results strongly indicate that human IGF-II is primarily produced in paraganglionic tissues and tumors.