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Cyr61-positive cancer stem-like cells enhances distal metastases of pancreatic cancer

2016; Impact Journals LLC; Volume: 7; Issue: 45 Linguagem: Inglês

10.18632/oncotarget.12248

1949-2553

Weidong Shi, Chenyue Zhang, Zhen Chen, Hao Chen, Luming Liu, Zhiqiang Meng,

Hedgehog Signaling Pathway Studies

// Weidong Shi 1, 2, 3 , Chenyue Zhang 1, 2 , Zhen Chen 1, 2, 3 , Hao Chen 1, 2, 3 , Luming Liu 1, 2 , Zhiqiang Meng 1, 2, 3 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China Correspondence to: Zhiqiang Meng, email: mengzhq@yeah.net Keywords: Cyr61, cancer stem-like cells, metastases, pancreatic cancer Received: May 26, 2016 Accepted: September 16, 2016 Published: September 26, 2016 ABSTRACT 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.