Modulation of a membrane-associated marker in progenitor cells of human pancreas carcinoma

For the identification of early steps in the multiphasic process of human pancreas carcinogenesis we have developed a panel of monoclonal antibodies to normal and carcinogen-treated human pancreas cells. One of these, an IgG3 with strong affinity for a membrane-associated 46 kd protein (p-46) in progenitor cells of methylnitrosourea (MNU)-treated human pancreas, was purified by h.p.l.c. and used to study the modulation of this marker in human pancreas carcinogenesis. This protein was undetectable in adult human pancreas, appeared on the cell surface of a small subpopulation of human pancreas explants exposed to MNU, persisted in proliferating cells in hyperplastic foci, and was abundant in anaplastic cells in this model. This marker was associated with cytoplasmic and nuclear membrane of all cells in non-tumorigenic and tumorigenic cell lines derived from these explants. It was present in primary carcinomas of human pancreas but absent in normal pancreas adjacent to tumors. This p-46 marker appears to be organ and species specific since it was undetectable in other normal tissues and their neoplastic counterparts.