Cyr61-positive cancer stem-like cells enhances distal metastases of pancreatic cancer.
Cyr61-positive cancer stem-like cells enhances distal metastases of pancreatic cancer.
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Cyr61阳性癌症干细胞样细胞增强胰腺癌的远端转移
DOI：
10.18632/oncotarget.12248
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Meng Z
中科院分区：
文献类型：
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作者：
Shi W;Zhang C;Chen Z;Chen H;Liu L;Meng Z
原发性肿瘤切除后有效抑制肿瘤转移是癌症治疗的关键。我们最近发现Cyr 61通过PI 3 k/Akt信号增强p27的核排斥促进胰腺导管腺癌（PDAC）的生长。在这里，我们报告说，管理的腺相关病毒载体携带短发夹干扰RNA（shRNA）的Cyr 61通过胰管显着减少远端肿瘤转移后切除原发性胰腺肿瘤小鼠。此外，PDAC细胞中Cyr 61的去除显著抑制体外肿瘤球的形成，显著降低皮下移植肿瘤的生长，并显著降低连续过继移植到NOD/SCID小鼠后肿瘤形成的发生率。最后，与诊断时没有转移的PDAC相比，在来自具有远端肿瘤转移的患者的PDAC标本中检测到更高的Cyr 61水平。总之，我们的研究表明，在PDAC中抑制癌症干细胞样细胞中的Cyr 61可以抑制原发性肿瘤切除后的肿瘤细胞转移。
Efficient inhibition of tumor metastasis after resection of primary tumors is critical for cancer therapy. We have recently shown that Cyr61 promotes growth of pancreatic ductal adenocarcinoma (PDAC) through PI3k/Akt signaling-enhanced nuclear exclusion of p27. Here, we report that administration of adeno-associated viral vectors carrying a short-hairpin interfering RNA (shRNA) for Cyr61 via pancreatic duct significantly decreased the distal tumor metastases after resection of primary pancreatic tumor in mice. Moreover, Cyr61 depletion in PDAC cells significantly inhibited the tumor sphere formation in vitro, significantly decreased the growth of the subcutaneously transplanted tumor, and significantly decreased the incidence of tumor formation after serial adoptive transplantation into NOD/SCID mice. Finally, higher Cyr61 levels were detected in the PDAC specimens from the patients with distal tumor metastasis, compared to PDAC without metastasis at diagnosis. Together, our study suggests that suppression of Cyr61 in cancer stem cell-like cells in PDAC may inhibit tumor cell metastasis after resection of the primary tumor.