ESTABLISHMENT AND CHARACTERIZATION OF 2 CELL-LINES WITH DIFFERENT GRADE OF DIFFERENTIATION DERIVED FROM ONE PRIMARY HUMAN PANCREATIC ADENOCARCINOMA

From a liver metastasis of a human pancreatic adenocarcinoma, we have established cell lines for studying the cell biology of this tumor. We obtained two cell lines with different morphological, chromosomal and functional properties. One of them, named PaTu 8988s, revealed a solid growth in nude mouse xenografts with cells exhibiting only occasional polar organisation of the cytoplasm. In general, no apical or basolateral plasma membrane domains could be distinguished and the sparse organelles were randomly distributed throughout the cytoplasm. Secretory products, such as mucin, were weakly stained histochemically or were completely absent. Transglutaminase (TGase) activity used as a marker for cellular differentiation was low in these cells. The other cell line, named PaTu 8988t, grew tumors composed of tubular structures when injected subcutaneously into nude mice. Cells were polarized with distinct apical and basolateral plasma membranes and the cytoplasmatic organelles were arranged with the nucleus in the lower part of the cell, while the apical cytoplasm contained the Golgi complex and numerous secretion granules. A high content of mucin was stained histochemically and transglutaminase activity was ten times higher than in PaTu 8988s. Comparing the chromosome number per metaphase plate, both cell lines showed a major peak, with 45-55 chromosomes per metaphase plate in PaTu 8988s and about 110-120 chromosomes per metaphase plate in PaTu 8988t. When the two cell lines were injected intraveneously into the tail vein of nude mice, only PaTu 8988s developed metastases localized exclusively in the lung, whereas PaTu 8988t produced no metastases in any organ. We conclude, that two cell lines exhibiting different grades of differentiation as well as a different potency to metastasize can be established from the same primary tumor, and that these cell lines represent a suitable model for further study of the cell biology of human pancreatic adenocarcinoma.