Expression of annexin II and stromal tenascin C promotes epithelial to
mesenchymal transition and correlates with distant metastasis in pancreatic
cancer
#MMPMID29749431
Yoneura N
; Takano S
; Yoshitomi H
; Nakata Y
; Shimazaki R
; Kagawa S
; Furukawa K
; Takayashiki T
; Kuboki S
; Miyazaki M
; Ohtsuka M
Int J Mol Med
2018[Aug]; 42
(2
): 821-830
PMID29749431
show ga
The interaction between cancer cells and stromal components contributes to cancer
invasion and metastasis in pancreatic ductal adenocarcinoma (PDAC). The present
study investigated the role of the correlation between annexin II (ANX2) and
stromal tenascin C (TNC) with the progression of PDAC. The functions of the
expression ANX2 and TNC were assessed in in vitro experiments using mouse and
human PDAC cells, and the clinical effect was analyzed using immunohistochemistry
with surgically resected PDAC tissues. The effects on epithelial to mesenchymal
transition (EMT), invasion, putative cancer stemness, and anoikis resistance were
examined in vitro using murine precancerous pancreatic intraepithelial neoplasia
(PanIN) cells and murine and human invasive PDAC cells with ANX2 knockdown using
specific small interfering RNA (siRNA)s and recombinant TNC (rTNC). ANX2 was
expressed at a high level in primary PanIN cells and invasive PDAC cells,
compared with the levels in liver metastatic PDAC cells. In the ANX2?knockdown
cells, there were fewer cells with a morphological mesenchymal appearance in
three?dimensional culture and invasion was reduced compared with that in the
control cells. Morphological change into the mesenchymal phenotype and invasion
were enhanced by rTNC treatment in the control PDAC cells but not in the
ANX2?knockdown cells. Pancreatosphere formation assays showed that ANX2 and TNC
facilitated the maintenance of stem?like characters in PDAC cells. Furthermore,
anoikis assays indicated that the interaction of ANX2?TNC contributed to anoikis
resistance in PDAC cells. In the immunohistochemistry analyses, the group with a
high expression of ANX2 and high stromal TNC was significantly correlated with
distant metastasis, and was associated with hematogenous/peritoneal recurrence
and poor outcomes following surgery in resected human primary PDAC tissues. In
conclusion, the results demonstrated that ANX2 and stromal TNC regulated invasion
in addition to stemness and anoikis resistance, which are crucial for metastasis
in the progression of PDAC. These results indicate the potential of the ANX2?TNC
axis as a therapeutic target for PDAC metastasis.
free
free
free
