KiSS-1-mediated suppression of the invasive ability of human pancreatic carcinoma cells is not dependent on the level of KiSS-1 receptor GPR54

• Published in: Molecular medicine reports Vol. 13; no. 1; pp. 123 - 129
• Main Authors: WANG, CHUN-HUI, QIAO, CHONG, WANG, RUO-CHEN, ZHOU, WEN-PING
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.01.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Cancer therapies; Care and treatment; Cell culture; Cell Line, Tumor; Cell Proliferation; China; Complications and side effects; Diagnosis; Gene Expression Regulation, Neoplastic; Gene therapy; GPR54; Health aspects; Humans; invasion; Invasiveness; KiSS-1; Kiss1 protein; Kisspeptins - metabolism; Laboratories; Lymph nodes; Metastases; Metastasis; Mortality; Neoplasm Invasiveness; Pancreatic cancer; Pancreatic carcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Penicillin; Peptides; Polymerase chain reaction; proliferation; Proteins; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Kisspeptin-1; Reverse transcription; Risk factors; Studies; Transfection; Trophoblasts; Tumor cell lines; Western blotting; China; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2015.4535

The onset of local invasion and lymphatic metastasis in pancreatic cancer limits survival following surgical intervention and additional therapies. Reduced expression of KiSS-1 in pancreatic cancer is associated with cancer metastasis. Previous studies have indicated that kisspeptin, the KiSS-1 peptide, is able to bind to its receptor-GPR54 (hOT7T175) and suppress the migration of PANC-1 pancreatic cancer cells. Whether the metastatic suppression of KiSS-1 is dependent on the levels of GPR54 in pancreatic cancer cell lines remains unclear. Human BxPC-3 pancreatic carcinoma cells are highly differentiated without exhibiting metastasis, however PANC-1 pancreatic carcinoma cells are poorly differentiated and exhibit local and lymph node metastasis. Compared with primary cultured trophoblasts, BxPc-3 and PANC-1 cells were observed to express low levels of KiSS-1 mRNA and protein, measured using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. However, greater mRNA and protein expression levels of GPR54 were observed in PANC-1 cells compared with BxPc-3 cells. An MTT assay was used to investigate the effect of KiSS-1 on BxPc-3 and PANC-1 cell proliferation. There were no significant differences in proliferation following transfection with KiSS-1 in BxPc-3 and PANC-1 cells compared with the controls (P>0.05). A Transwell assay with chambers coated with Matrigel was used to evaluate the in vitro invasive ability of BxPc-3 and PANC-1 cells, with the invasion index of BxPc-3 and PANC-1 cells significantly reduced following 48 h of KiSS-1 overexpression (P<0.05). The mRNA and protein expression levels of KiSS-1 were significantly increased in BxPc-3 and PANC-1 cells 48 h subsequent to transfection with KiSS-1 (P<0.05), while GPR54 expression was not altered (P>0.05). KiSS-1 is a metastasis suppressor gene of pancreatic cancer, and this suppression is not dependent on the expression levels of GPR54. Therefore, KiSS-1 is potentially a novel target for gene therapy.