Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis
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Arivajiagane Arundhathi1,4,*, Wen-Han Chuang1,*, Jen-Kun Chen2,*, Shin-E Wang3,*, Yi-Ming Shyr3, Jiun-Yu Chen2, Wei-Neng Liao2, Hsin-Wei Chen1, Yi-Min Teng1, Chiao-Chih Pai1, Chih-Hong Wang1
1Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
2Institute of Biomedical Engineering & Nanomedicine, National Health Research Institutes, Miaoli, Taiwan
3Department of General Surgery, Taipei Veterans General Hospital, and National Yang Ming University, Taipei, Taiwan
4Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu, Taiwan
*These authors have contributed equally to this work
Chih-Hong Wang, email: [email protected]
Keywords: prorenin receptor, pancreatic cancer, PanIN lesions, Kras, SPECT/CT
Received: August 21, 2015 Accepted: July 05, 2016 Published: July 13, 2016
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with 125I was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-KrasG12D mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that 125I-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-KrasG12D mice. Therefore, anti-PRR labelled with 125I is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer.
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