96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

differentiated and TNM stage III or IV tumours. p53 mutation was closely
related with the degree of differentiation, TNM stage, vessel invasion
and lymph node metastasis. By combining the results with microsatellite
changes and p53 mutation, NE and adenocarcinoma cells showed the
same MSI, LOH or p53 mutation in most cases (27/30). In the other three
cases, different MSI, LOH or p53 mutation occurred.
Conclusion. we suggest that, in 27 of 30 cases, NE and adenocarcinoma
cells were generated from the same stem cells. The multipotent stem cells
differentiate to NE and adenocarcinoma cells, initiated by hormonal
change, microenvironmental change, and genomic instability. NE cells
act as parenchyma of carcinoma, and excrete hormones to promote carcinoma.
The remaining three cases might have had different ancestral
cells, and this needs further study.
SG-P-122
IGFBP7 high expression in the colorectal cancer cells is related
to Wnt signaling pathway inhibition during the interactions
between colorectal cancer cells and fibroblasts
J . Xu1 , H . Deng* 1 , C . Rao1 , S . Lin1 1Zhejiang University, School of Medicine, Hangzhou, China
Aims. To study the Wnt signaling pathway in interactions between the
colorectal cancer cells and fibroblasts and its impact on the expression of
IGFBP7 (Insulin-like growth factor binding protein 7) in the colorectal
cancer cells.
Methods. Colorectal cancer cells SW480 or SW620 were cultured in
HELF cells or activated HELF cells conditional media, treated by Wnt
signaling pathway agonist (LiCl) or Wnt signaling pathway inhibitor
(DKK-1). RT-PCR, Real-time PCR, Western blot and immunofluorescence
microscopy were used to detect the related protein and target genes
of Wnt signaling pathway and the expression of IGFBP7.
Results. IGFBP7 expression was increased with times in the colorectal
cancer cells treated by the activated HELF conditional media. And activation
of Wnt signaling pathway reduced IGFBP7 expression, inhibition
of Wnt signaling pathway induced IGFBP7 expression.
Conclusions. The interactions between tumor cells and fibroblasts could
inhibit Wnt signaling pathway in the tumor cells, and induce the expression
of IGFBP7.
SG-P-123
TGF-beta and Wnt signaling pathways regulate the expression of
IGFBP7 of fibroblasts in the tumor-stroma interactions
C . Rao1 , J . Xu1 , M . Liu1 , H . Deng* 1
1Zhejiang University, School of Medicine, Hangzhou, China
Aims. To find out the mechanism of the up-regulation of IGFBP7and the
biological changes in fibroblasts during the interactions with colorectal
cancer cells.
Methods. Fibroblasts (HELFs) were cultured in colorectal cancer cells
conditioned media (SW620-CM), treated by TGF-beta1, TGF-beta1 receptor
antagonist (SB431542), TGF-beta1 specific antibody (AF), Wnt
signaling pathway agonist (LiCl) and inhibitor (DKK-1) respectively. Q-
PCR, Western Blot, ELISA, Immunofluorescence microscopy and flow
cytometry were used to detect the expression of related targeted genes
and proteins of TGF-beta and Wnt signaling pathways.
Results. HELFs cultured in SW620-CM were activated with abundant
expression of alfa-SMA and showed strong proliferation and weak apoptosis
and senescence. The expression of IGFBP7 of HELFs was up-regulated
in time-dependent and dose-dependent manners when cultured
with SW620-CM, while TGF-beta signaling were activated as Smad2,
P-Smad2 and TGF-beta R2 were up-regulated in HELFs. These effects
could be strengthened by TGF-beta1 and inhibited by SB431542 or AF.
During the interactions, the downstream genes of Wnt signaling pathway
such as c-myc, cyclinD1 were up-regulated and the proteins of
Wnt signaling pathway such as beta-catenin, Dvl3, Dvl2 and Naked2
were obviously up-regulated which suggested the canonical Wnt signaling
pathway was also activated.
Conclusions. TGF-beta and Wnt signaling pathways were activated during
colorectal cancer cells-fibroblasts interactions. Upregulating of
IGFBP7 in HELFs was mainly through TGF-beta1/ALK5/ Smad-2 signaling
pathway. Wnt signaling pathway may also play an important role
in this process.
SG-P-124
Serum MiR-192 and MiR-194 as tumor biomarker for pancreatic
ductal adenocarcinoma
J . Zhang1 , C .-y . Zhao1 , D .-h . Yu1 , Y . Chen1 , Q .-h . Liu1 , M . Shi1 , J .-t . Zhang1 , G . Jin1 ,
P . Cheng1 , X .-g . Hu1 , C .-r . Ni1 , M .-h . Zhu1 1Department of Pathology, Changhai Hospital, Shanghai, China
Aims. To assess the validity of using serum miRNA signatures of PDAC
as biomarkers for diagnosis.
Methods. MiRNA microarray was used to detect the differences between
PDAC samples and normal pancreatic tissues. MiR-192 and miR-194
were found in the tissues of human PDAC and in the explants in tumorbearing
SCID mice by locked nucleic acid-based in situ hybridization
(LNA-ISH). Serum levels of miR-192 and miR-194 in PDAC patients,
duodenal adenocarcinoma patients and healthy controls, as well as six
pancreatic cancer cell lines and their culture supernatants were determined
by real-time PCR.
Results. Eight miRNAs were found overexpressed and eight were lowly
expressed in PDAC tissues compared with those in the normal pancreatic
tissues. MiR-192 and miR-194 were found overexpressed in the tissues
of human PDAC and in the explants in tumor-bearing SCID mice.
The levels of miR-192 and miR-194 in the supernatants of six pancreatic
cancer cell lines were positively correlated with their cellular expressions
(r=0.849, p