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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Br+J+Cancer
2015 ; 112
(12
): 1944-50
Nephropedia Template TP
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English Wikipedia
Expression of E-cadherin repressors SNAIL, ZEB1 and ZEB2 by tumour and stromal
cells influences tumour-budding phenotype and suggests heterogeneity of stromal
cells in pancreatic cancer
#MMPMID25989272
Galván JA
; Zlobec I
; Wartenberg M
; Lugli A
; Gloor B
; Perren A
; Karamitopoulou E
Br J Cancer
2015[Jun]; 112
(12
): 1944-50
PMID25989272
show ga
BACKGROUND: There is evidence that tumour-stroma interactions have a major role
in the neoplastic progression of pancreatic ductal adenocarcinoma (PDAC). Tumour
budding is thought to reflect the process of epithelial-mesenchymal transition
(EMT); however, the relationship between tumour buds and EMT remains unclear.
Here we characterize the tumour-budding- and stromal cells in PDAC at protein and
mRNA levels concerning factors involved in EMT. METHODS: mRNA in situ
hybridisation and immunostaining for E-cadherin, ?-catenin, SNAIL1, ZEB1, ZEB2,
N-cadherin and TWIST1 were assessed in the main tumour, tumour buds and tumour
stroma on multipunch tissue microarrays from 120 well-characterised PDACs and
associated with the clinicopathological features, including peritumoural (PTB)
and intratumoural (ITB) budding. RESULTS: Tumour-budding cells showed increased
levels of ZEB1 (P<0.0001) and ZEB2 (P=0.0119) and reduced E-cadherin and
?-catenin (P<0.0001, each) compared with the main tumour. Loss of membranous
?-catenin in the main tumour (P=0.0009) and tumour buds (P=0.0053), without
nuclear translocation, as well as increased SNAIL1 in tumour and stromal cells
(P=0.0002, each) correlated with high PTB. ZEB1 overexpression in the main
tumour-budding and stromal cells was associated with high ITB (P=0.0084; 0.0250
and 0.0029, respectively) and high PTB (P=0.0005; 0.0392 and 0.0007,
respectively). ZEB2 overexpression in stromal cells correlated with higher pT
stage (P=0.03), lymphatic invasion (P=0.0172) and lymph node metastasis
(P=0.0152). CONCLUSIONS: In the tumour microenvironment of phenotypically
aggressive PDAC, tumour-budding cells express EMT hallmarks at protein and mRNA
levels underlining their EMT-type character and are surrounded by stromal cells
expressing high levels of the E-cadherin repressors ZEB1, ZEB2 and SNAIL1, this
being strongly associated with the tumour-budding phenotype. Moreover, our
findings suggest the existence of subtypes of stromal cells in PDAC with
phenotypical and functional heterogeneity.