Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer.
Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer.
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DOI：
10.3892/ijmm.2018.3652
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发表时间：
2018-08
影响因子：
5.4
通讯作者：
Ohtsuka M
中科院分区：
文献类型：
--
作者：
Yoneura N;Takano S;Yoshitomi H;Nakata Y;Shimazaki R;Kagawa S;Furukawa K;Takayashiki T;Kuboki S;Miyazaki M;Ohtsuka M
胰腺导管腺癌（PDAC）中癌细胞和间质成分之间的相互作用有助于癌症的侵袭和转移。本研究探讨了膜联蛋白II（ANX 2）和基质生腱蛋白C（TNC）与PDAC进展之间的相关性。使用小鼠和人PDAC细胞在体外实验中评估ANX 2和TNC表达的功能，并使用手术切除的PDAC组织的免疫组织化学分析临床效果。使用小鼠癌前胰腺上皮内瘤变（PanIN）细胞以及使用特异性小干扰RNA（siRNA）和重组TNC（rTNC）敲低ANX 2的小鼠和人侵袭性PDAC细胞，在体外检查对上皮向间质转化（EMT）、侵袭、推定癌症干性和失巢凋亡抗性的影响。ANX 2在原代PanIN细胞和侵袭性PDAC细胞中的表达水平高于肝转移性PDAC细胞。与对照细胞相比，在ANX 2敲除细胞中，三维培养中具有形态学间充质外观的细胞较少，侵袭性也减少。在对照PDAC细胞中，rTNC处理增强了间充质表型的形态变化和侵袭，但在ANX 2敲低细胞中没有。胰腺球形成试验表明ANX 2和TNC促进PDAC细胞中干细胞样特征的维持。此外，失巢凋亡实验表明ANX 2-TNC的相互作用有助于PDAC细胞的失巢凋亡抵抗。在免疫组织化学分析中，ANX 2高表达和高基质TNC的组与远处转移显著相关，并且与切除的人原发性PDAC组织中的手术后的血源性/腹膜复发和不良结局相关。总之，结果表明，ANX 2和间质TNC除了调节干性和失巢凋亡抗性之外还调节侵袭，这对于PDAC进展中的转移至关重要。这些结果表明ANX 2-TNC轴作为PDAC转移的治疗靶标的潜力。
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.
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影响因子：
--
作者：
Suzuki K;Takano S;Yoshitomi H;Nishino H;Kagawa S;Shimizu H;Furukawa K;Miyazaki M;Ohtsuka M
通讯作者：
Ohtsuka M
DOI：
10.1073/pnas.0912589107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Rovira, Meritxell;Scott, Sherri-Gae;Leach, Steven D.
通讯作者：
Leach, Steven D.
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
3.3
作者：
Wescott, Melanie P.;Rovira, Meritxell;Rustgi, Anil K.
通讯作者：
Rustgi, Anil K.