Epithelial-mesenchymal transition and mesenchymal-epithelial transition via regulation of ZEB-1 and ZEB-2 expression in pancreatic cancer.
BACKGROUND AND OBJECTIES: Phenotypic plasticity of cancer cells via epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) is essential for tumor progression and metastasis.


METHODS
Tissue samples were obtained from 76 pancreatic head cancers. We assessed the expression of E-cadherin, vimentin, ZEB-1, and ZEB-2 by immunohistochemical and immunofluorescence staining. Next, 147 metastatic lymph nodes from 45 pancreatic cancers with low expression of E-cadherin were obtained and divided into two categories according to the maximum diameter of the metastases: 2 mm or more and less than 2 mm.


RESULTS
High expressions of ZEB-1 and ZEB-2 in the primary tumors were significantly associated with repression of E-cadherin (P = 0.0007), and poorer prognosis (P = 0.0322). Forty-three (29.3%) of the 147 metastatic tumors from pancreatic cancers with low expression of E-cadherin showed high E-cadherin expression. Cancer cells in the larger metastases showed high expression of E-cadherin (P = 0.0061) and low expression of ZEB-1 (P = 0.0170) and ZEB-2 (P = 0.0036) compared with those in the smaller metastases.


CONCLUSIONS
In primary pancreatic tumors and metastatic lymph nodes, high and low expression of ZEB-1 and ZEB-2 was associated with mesenchymal and epithelial phenotype of cancer cells, respectively.
Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan. h-krhr@m3.kufm.kagoshima-u.ac.jp
Hiroshi
H
Kurahara
Sonshin
S
Takao
Kosei
K
Maemura
Yuko
Y
Mataki
Taisaku
T
Kuwahata
Koki
K
Maeda
Qiang
Q
Ding
Masahiko
M
Sakoda
Satoshi
S
Iino
Sumiya
S
Ishigami
Shinichi
S
Ueno
Hiroyuki
H
Shinchi
Shoji
S
Natsugoe
D000368:Aged; D015820:Cadherins / Q000032:analysis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D012097:Repressor Proteins / Q000032:analysis* / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis* / Q000502:physiology; D014746:Vimentin / Q000032:analysis; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014746:Vimentin; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1