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pancreatic cancer EMT

Wei Li, Zhengdong Jiang, Xue Xiao, Zheng Wang, Zheng Wu, Qingyong Ma, Lei Cao
Curcumin is a natural polyphenol compound derived from turmeric. It possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and anti-tumor progression properties. Our recent study demonstrated that superoxide dismutase (SOD)-dependent production of hydrogen peroxide (H2O2) promoted the invasive and migratory activity of pancreatic cancer cells. However, whether curcumin suppresses SOD-induced cancer progression and the related mechanisms remains unclear. Since epithelial‑to-mesenchymal transition (EMT) plays a key role in tumor metastasis, the aim of the present study was to examine whether curcumin intervenes with SOD-induced EMT in pancreatic cancer and the underlying mechanism...
March 1, 2018: International Journal of Oncology
Ke Chen, Liang Cheng, Weikun Qian, Zhengdong Jiang, Liankang Sun, Yanfei Zhao, Yongsheng Zhou, Lizhi Zhao, Pengli Wang, Wanxing Duan, Qingyong Ma, Wei Yang
Pancreatic cancer is the fourth leading cause of cancer-associated mortality worldwide, with an overall 5-year survival rate <8%. We studied the therapeutic effect of itraconazole (ITZ), a commonly used broad-spectrum anti-fungal agent, in the treatment of pancreatic cancer, and to reveal the underlying anticancer mechanisms. Effects of ITZ on cell proliferation, apoptosis, invasion and migration were observed by MTT assays and colony formation assays, flow cytometry, wound scratch assays and transwell assays, respectively...
February 26, 2018: Oncology Reports
Song-Ming Ding, Ai-Li Lu, Wu Zhang, Lin Zhou, Hai-Yang Xie, Shu-Sen Zheng, Qi-Yong Li
Background: Our previous study showed that cancer-associated fibroblast MRC-5 promoted hepatocellular carcinoma progression by enhancing migration and invasion capability. However, few studies have explored the role of MRC-5 in pancreatic cancer (PC). In this study, we examined the exact role and associated mechanisms of MRC-5. Methods: The conditioned media for MRC-5 was used to culture PC cell lines SW1990 and PANC-1. Cell proliferation was compared based on colony formation assays of PC cells in normal media and of PC cells cultured with conditioned media of MRC-5...
2018: Journal of Cancer
Yoko Fujii-Nishimura, Ken Yamazaki, Yohei Masugi, Junya Douguchi, Yutaka Kurebayashi, Naoto Kubota, Hidenori Ojima, Minoru Kitago, Masahiro Shinoda, Akinori Hashiguchi, Michiie Sakamoto
Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding "focal differentiation" in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues...
February 19, 2018: Pathology International
Norihiko Sasaki, Toshiyuki Ishiwata, Fumio Hasegawa, Masaki Michishita, Hiroki Kawai, Yoko Matsuda, Tomio Arai, Naoshi Ishikawa, Junko Aida, Kaiyo Takubo, Masashi Toyoda
The expression of ATP-binding cassette subfamily G member 2 (ABCG2) is related with tumorigenic cancer stem cells (CSCs) in several cancers. However, the effects of ABCG2 on CSC-related malignant characteristics in pancreatic ductal adenocarcinoma (PDAC) are not well elucidated. In this study, we compared the characteristics of low (ABCG2-) and high (ABCG2+)-ABCG2-expressing PDAC cells after cell sorting. In adherent culture condition, human PDAC cells, PANC-1, contained approximately 10% ABCG2+ cell populations, and ABCG2+ cells displayed more and longer microvilli compared with ABCG2- cells...
February 14, 2018: Cancer Science
Meng Zhou, Youli Zhang, Hong Wei, Junbo He, Dawei Wang, Baoding Chen, Jian Zeng, Aihua Gong, Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit-8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial-mesenchymal transition (EMT) and the Hippo-yes-associated protein (YAP) pathway were detected using western blot analysis...
March 2018: Oncology Letters
Ye Rim Chang, Taesung Park, Sung Hyo Park, Yong Kang Kim, Kyoung Bun Lee, Sun-Whe Kim, Jin-Young Jang
There is an urgent need to investigate the genetic changes that occur in intraductal papillary mucinous neoplasm (IPMN), which is a well-known precursor of pancreatic cancer. In this study, gene expression profiling was performed by removing unwanted variation to determine the differentially expressed genes (DEGs) associated with malignant progression of IPMN. Among the identified DEGs, zinc finger E-box binding homeobox 1 (ZEB1) and E-cadherin, a crucial regulator of epithelial-to-mesenchymal transition (EMT), was validated among identified DEGs...
January 2, 2018: Oncotarget
Ding-Wei Chen, Hong Wang, Ya-Fang Bao, Kun Xie
Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit‑8 assay, invasion assay, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2)...
January 26, 2018: Molecular Medicine Reports
Xinlu Liu, Xiaodong Tan, Peng Liu, Yunhao Wu, Songying Qian, Xiaobo Zhang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors known, with an overall 5-year survival rate of less than 6% due to early local invasion and distant metastasis. Exploring suitable therapeutic targets associated with invasion and metastasis is required for improving the prognosis of PDAC. In this study, we investigated the role of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) in PDAC. PGAM1 expression was examined in tissue samples of 54 PDAC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined...
January 31, 2018: Oncology Research
Hao Hu, Yandong Wang, Xiangya Ding, Yuan He, Zipeng Lu, Pengfei Wu, Lei Tian, Hao Yuan, Dongfang Liu, Guodong Shi, Tianfang Xia, Jie Yin, Baobao Cai, Yi Miao, Kuirong Jiang
BACKGROUND: Long non-coding RNAs (lncRNAs) play an important role in the development and progression of various tumors, including pancreatic cancer (PC). Recent studies have shown that lncRNAs can 'act in cis' to regulate the expression of its neighboring genes. Previously, we used lncRNAs microarray to identify a novel lncRNA termed XLOC_000647 that was down-regulated in PC tissues. However, the expression and function of XLOC_000647 in PC remain unclear. METHODS: The expression of XLOC_000647 and NLRP3 in PC specimens and cell lines were detected by quantitative real-time PCR...
January 31, 2018: Molecular Cancer
Weiliang Jiang, Qiongying Yuan, Yuanye Jiang, Li Huang, Congying Chen, Guoyong Hu, Rong Wan, Xingpeng Wang, Lijuan Yang
Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down-regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo...
January 25, 2018: Journal of Cellular and Molecular Medicine
Heather K Schofield, Jörg Zeller, Carlos Espinoza, Christopher J Halbrook, Annachiara Del Vecchio, Brian Magnuson, Tania Fabo, Ayse Ece Cali Daylan, Ilya Kovalenko, Ho-Joon Lee, Wei Yan, Ying Feng, Saadia A Karim, Daniel M Kremer, Chandan Kumar-Sinha, Costas A Lyssiotis, Mats Ljungman, Jennifer P Morton, Stefanie Galbán, Eric R Fearon, Marina Pasca di Magliano
Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras...
January 25, 2018: JCI Insight
Hung-Yi Liu, Murray Korc, Chien-Chi Lin
The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening...
January 8, 2018: Biomaterials
Luguang Chen, Chao Ma, Yun Bian, Chengwei Shao, Tiegong Wang, Jing Li, Xiaodan Chong, Li Su, Jianping Lu
Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues...
December 19, 2017: Oncotarget
Muxing Kang, Wen Zheng, Qing Chen, Wenjie Qin, Pengping Li, Shifei Huang, Yizhao Zhou, Lantian Wang, Haolei Cai, Wenjie Lu, Biao Jiang, Qingqu Guo, Jian Chen, Dylan Wan, Jianyu Rao, Yulian Wu
As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA. Protein and mRNA expression level of TS were evaluated in en bloc PDA samples, the prognostic effect of TS expressed in cytoplasm or cytonuclear was determined separately in the first time...
January 10, 2018: Cancer Letters
Ji-Hyun Lee, Seul-Ki Kim, Iftikhar Ali Khawar, Su-Yeong Jeong, Seok Chung, Hyo-Jeong Kuh
BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (microchannel) devices has proven to be a useful in studying cellular interactions and drug sensitivity. Here we present a microchannel plate-based co-culture model that integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix to mimic the tumor microenvironment in vivo by recapitulating epithelial-mesenchymal transition and chemoresistance...
January 12, 2018: Journal of Experimental & Clinical Cancer Research: CR
Ling Ma, Feng Wang, Chong Du, Zhengkui Zhang, Huahu Guo, Xuehai Xie, Hongqiao Gao, Yan Zhuang, Marko Kornmann, Hong Gao, Xiaodong Tian, Yinmo Yang
Long non-coding RNA (lncRNA) MEG3 has been demonstrated to be a tumour suppressor in many malignancies. However, the functional role of MEG3 in pancreatic cancer (PC) is unclear. In this study, the expression pattern of MEG3 was evaluated in 25 samples of microdissected PC tissues and 8 PC cell lines and was compared to the expression in adjacent non‑cancerous tissues and a human pancreatic normal epithelial cell line. Loss of MEG3 expression was observed in both the cancerous tissues and cancer cell lines...
January 2, 2018: Oncology Reports
Kege Yang, Yaqing Li, Guoda Lian, Haoming Lin, Changzhen Shang, Linjuan Zeng, Shaojie Chen, Jiajia Li, Chumei Huang, Kaihong Huang, Yinting Chen
Oncogenic KRAS plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. However, the mechanism has not been clearly elucidated. RKIP is a tumor repressor, and loss of RKIP has been shown in PDAC. Here, we found that KRAS expression was inversely correlated with RKIP expression in PDAC fresh tissue regardless of the KRAS mutant status. The negative correlation between KRAS and RKIP was further confirmed in our PDAC tissue microarray. KRAS overexpression and RKIP downregulation were associated with poor clinical outcomes...
January 8, 2018: International Journal of Cancer. Journal International du Cancer
Yue-Ming He, Yu-Sha Xiao, Lei Wei, Jia-Qiang Zhang, Cheng-Hong Peng
This study determines whether cullin 4B (CUL4B) promotes pancreatic cancer (PC) metastasis by inducing epithelial-mesenchymal transition (EMT) via the Wnt/β-catenin signaling pathway. Sixty-four PC patients were enrolled in this study. Human PC cell lines were distributed into blank, negative control, shCUL4B, PLOC, PLOC-CUL4B and PLOC-CUL4B + siRNA-β-catenin groups. The expressions of CUL4B, Wnt/β-catenin signaling pathway-related proteins, and EMT-related proteins were determined using RT-qPCR and western blotting...
December 23, 2017: Journal of Cellular Biochemistry
Kaja Lund, Cathrine Elisabeth Olsen, Judith Jing Wen Wong, Petter Angell Olsen, Nina Therese Solberg, Anders Høgset, Stefan Krauss, Pål Kristian Selbo
BACKGROUND: Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. METHODS: 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS2a and to investigate the effect of photodamage of lysosomes...
December 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
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