Monocyte-related functions expressed in cell lines established from human pancreatic adenocarcinoma. I. Comparative analysis of endocytotic activity, lysosomal enzyme secretion, and superoxide anion production.

: Fine structural analyses of human pancreatic carcinoma have demonstrated their composition of one major cell type, a mucin secreting cell. In lower grades of differentiation the tumor cells change polarity and reduce mucin production and secretion. Instead numerous small vesicles in the cytoplasm and a high frequency of coated pits and coated vesicles beneath the plasma membrane suggest endocytotic activity. One monoclonal antibody (BW 227/19) produced against pancreatic tumor cells of low differentiation, besides binding to primary pancreatic carcinoma in cytofluorometric studies, also reacted with 80% blood monocytes and with macrophages in a variety of tissues, indicating common antigenic determinants on both cell types. Therefore, monocyte-related functions--endocytosis, lysosomal enzyme secretion, and superoxide anion production--were measured in 5 cell lines of pancreatic carcinomas (two lines established from adenocarcinoma of the colon, two lines from small lung cell carcinomas, and one line from squamous cell carcinoma of the lung). These functions were measured under basal conditions and after exposure to zymosan or immune complexes and were compared to isolated normal monocytes of the human. Endocytotic activity, as measured by the uptake of radiolabeled colloidal gold in 4 out of 5 pancreatic tumor cell lines, showed 50% of the basal activity of monocytes, while other tumor cells had only 20% of this activity. Only pancreatic tumor cells demonstrated increased endocytotic, secretory, and chemiluminescence activity to a similar extent as human monocytes after exposure to zymosan or immune complexes. Fine structural studies using cationized ferritin demonstrated the regular endocytotic pathway with uptake via coated pits and vesicles into endosomes and their transfer to a membrane compartment associated with the Golgi complex. The findings indicate a striking similarity between pancreatic tumor cells in vitro and human monocytes, which could be of importance in the understanding of the biology of these ill-defined tumor cells.