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

被引:5
作者
Paddenberg, R
Flocke, K
Elsässer, HP
Lesch, G
Heidtmann, HH
Mannherz, HG
机构
[1] Ruhr Univ Bochum, Dept Anat & Embryol, Cell Biol Lab, D-4630 Bochum, Germany
[2] Univ Marburg, Inst Cytobiol & Cytopathol, Marburg, Germany
[3] Univ Marburg, Dept Internal Med, D-3550 Marburg, Germany
关键词
laminin-1; nidogen; human pancreatic tumour cell lines; cell polarity; vacuolar apical compartment;
D O I
10.1016/S0171-9335(98)80003-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A cell line (PaTu 8902LM) exhibiting an altered phenotypic appearance was selected from a highly dedifferentiated established human pancreatic tumour cell line (PaTu 8902) 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 genetically very closely related. The original PaTu 8902 line consisted of nat cells growing in monolayers. In contrast, the obtained PaTu 8902LM cells exhibited a spherical morphology and tended to form clusters. Immunofluorescence analysis using antibodies against apical and basolateral marker enzymes indicated that the PaTu 8902LM cells 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 cell 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 cell line formed solid tumours composed 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 stable transdifferentiation towards the phenotype of the epithelial cells 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 cell system in future analyses of the biology of pancreatic tumours which are of increasing incidence and clinical importance.
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收藏
页码:251 / 264
页数:14
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