Phenotypical changes of a human pancreatic adenocarcinoma cell line after selection on laminin-1/nidogen (LM/Ng) substratum

A cell line (PaTh 8902LM) exhibiting an altered phenotypic appearance was selected from a highly dedifferentiated established human pancreatic tumour cen line (PaTu 89(2) by repetitive exposure to laminin-1/nidogen substratum and subsequent selection for adherent cells. Polymerase chain reaction analysis for repetitive DNA indicated that both cell lines are geneticaUy very closely related. The original PaTu 8902 line consisted of flat cens growing in monolayers. In contrast, the obtained PaTu 8902LM cens exhibited a spherical morphology and tended to form clusters. Immunofluorescence analysis using antibodies against apical and basolateral marker enzymes indicated that the PaTu 8902LM cens were polarized, arranging their apical surfaces around central lumenal structures when growing in clusters. In addition, the selected PaTu 8902LM cell line exhibited altered levels of a number of differentiation marker enzymes like 5'-nucleotidase, transglutaminase and plasminogen activators. The different morphological characteristics of both cen lines were maintained even after injection into nude mice. In xenografts, PaTu 8902LM cells were grouped around lumenal, duct-like structures, whereas the original PaTu 8902 cen line formed solid tumours composed of undifferentiated cells. Evidence is presented that the PaTu 8902LM cens are not merely selected from preexisting ceUs, but that the exposure of PaTu 8902 cells to laminin-1/nidogen had induced a stable transdifferentiation towards the phenotype of the epithelial cens lining the pancreatic secretory ducts. Thus the PaTu 8902LM cells resemble more closely those cells from which tumours of the pancreas originate in vivo and therefore might be a useful cen system in future analyses of the biology of pancreatic tumours which are of increasing incidence and clinical importance.