PMID- 10415853
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 880
DP  - 1999 Jun 30
TI  - Hollow-spheres: a new model for analyses of differentiation of pancreatic duct 
      epithelial cells.
PG  - 83-93
AB  - We discovered a unique feature of a subclone of the pancreatic carcinoma cell 
      line A818. A818-1-derived hollow-spheres developed under three-dimensional growth 
      conditions. Hollow-spheres consist of a single layer of 50-200 epithelial cells 
      surrounding an inner lumen. In contrast to A818-1, the subclone A818-4 and all 
      other pancreatic tumor cell lines tested (n = 5), formed spheroids as the only 
      three-dimensional phenotype. A dramatically reduced proliferation rate compared 
      to the corresponding monolayer was observed in hollow-spheres when 
      bromodeoxyuridine (BrdU) incorporation was measured. This finding was confirmed 
      by immunostaining using the MIB-1 antibody. Mechanically disrupted hollow-spheres 
      not only attached but also grew as monolayer with the same doubling time as the 
      founder cells. Hollow-spheres developed in fetal calf serum (FCS) containing RPMI 
      1640 medium without additionally added cytokines. A818-1 hollow-sphere formation 
      and integrity was influenced by interferon-gamma. Tumor necrosis factor-alpha 
      (TNF-alpha) led to cell death. Exogenously added hepatocyte growth factor (HGF) 
      showed no effect neither on hollow-sphere formation nor on the integrity of 
      completely developed hollow-spheres. Moreover, no changes were observed when 
      cells were treated with a neutralizing antibody for HGF. Interestingly, 
      hollow-spheres showed intensive immunoreactivity for the HGF-receptor (c-met) and 
      its ligand (HGF). Immunostaining for the biliary glycoprotein (BGP), the 
      non-specific cross-reacting antigen 95 (NCA95) and beta-catenin revealed a polar 
      organization of hollow-spheres. Immunhistochemically, hollow-spheres were 
      negative for the carcinoembryonic antigen (CEA). When hollow-spheres were 
      embedded into matrigel, duct-like tubes grew out. Taken together, A818-1 
      hollow-spheres resemble normally differentiated duct-like structures and will 
      serve as an excellent model to study differentiation of human pancreatic 
      epithelial cells.
FAU - Lehnert, L
AU  - Lehnert L
AD  - Department of Molecular Oncology, Christian Albrechts University of Kiel, 
      Germany.
FAU - Trost, H
AU  - Trost H
FAU - Schmiegel, W
AU  - Schmiegel W
FAU - Roder, C
AU  - Roder C
FAU - Kalthoff, H
AU  - Kalthoff H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Aged
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cell Polarity
MH  - Epithelial Cells/cytology/drug effects
MH  - Female
MH  - Humans
MH  - Interferon-gamma/pharmacology
MH  - Models, Biological
MH  - Pancreatic Ducts/*cytology
MH  - Pancreatic Neoplasms/*pathology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1999/07/23 00:00
MHDA- 1999/07/23 00:01
CRDT- 1999/07/23 00:00
PHST- 1999/07/23 00:00 [pubmed]
PHST- 1999/07/23 00:01 [medline]
PHST- 1999/07/23 00:00 [entrez]
AID - 10.1111/j.1749-6632.1999.tb09512.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 1999 Jun 30;880:83-93. doi: 10.1111/j.1749-6632.1999.tb09512.x.