PHENOTYPICAL CHANGES OF A HUMAN PANCREATIC ADENOCARCINOMA CELL-LINE AFTER SELECTION ON LAMININ-1 NIDOGEN (LM/NG) SUBSTRATUM/

A cell line (PaTu 8902LM) exhibiting an altered phenotypic appearance was selected from a highly dedifferentiated established human pancreat ic tumour cell line (PaTu 8902) by repetitive exposure to laminin-1/ni dogen substratum and subsequent selection for adherent cells. Polymera se chain reaction analysis for repetitive DNA indicated that both cell lines are genetically very closely related. The original PaTu 8902 li ne consisted of nat cells growing in monolayers. In contrast, the obta ined PaTu 8902LM cells exhibited a spherical morphology and tended to form clusters. Immunofluorescence analysis using antibodies against ap ical and basolateral marker enzymes indicated that the PaTu 8902LM cel ls were polarized, arranging their apical surfaces around central lume nal structures when growing in clusters. In addition, the selected PaT u 8902LM cell line exhibited altered levels of a number of differentia tion marker enzymes like 5'-nucleotidase, transglutaminase and plasmin ogen activators. The different morphological characteristics of both c ell lines were maintained even after injection into nude mice. In xeno grafts, PaTu 8902LM cells were grouped around lumenal, duct like struc tures, whereas the original PaTu 8902 cell line formed solid tumours c omposed of undifferentiated cells. Evidence is presented that the PaTu 8902LM cells are not merely selected from preexisting cells, but that the exposure of PaTu 8902 cells to laminin-1/nidogen had induced a st able transdifferentiation towards the phenotype of the epithelial cell s lining the pancreatic secretory ducts. Thus the PaTu 8902LM cells re semble more closely those cells from which tumours of the pancreas ori ginate in vivo and therefore might be a useful cell system in future a nalyses of the biology of pancreatic tumours which are of increasing i ncidence and clinical importance.