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Vedanta Mehta, Laura Fields, Ian M Evans, Maiko Yamaji, Caroline Pellet-Many, Timothy Jones, Marwa Mahmoud, Ian Zachary
OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Qi Liu, Jianwu Jiang, Yang Fu, Tao Liu, Yang Yu, Xiefu Zhang
MicroRNAs (miRNAs) are identified as key regulators in cancer initiation, progression and metastasis including gastric cancer (GC). The aim of the study is to explore clinical significance and potential mechanism of miR-129-5p in GC development. In the study, our results found that miR-129-5p expression was significantly downregulated in GC tissues, compared with adjacent normal tissues using qRT-PCR analyses. Furthermore, lower miR-129-5p expression closely associated with tumor size and lymph node invasion and poor prognosis of GC patients...
June 4, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiaoyun Wang, Francesca Polverino, Joselyn Rojas-Quintero, Duo Zhang, José Sánchez, Ilyas Yambayev, Eva Lindqvist, Robert Virtala, Ratko Djukanovic, Donna E Davies, Susan Wilson, Rory O'Donnell, Danen Cunoosamy, Petra Hazon, Andrew Higham, Dave Singh, Henric Olsson, Caroline A Owen
INTRODUCTION: Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice. METHODS: ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wild-type (WT) mice. WT and Adam9-/- mice were exposed to air or CS for 1-6 months, and COPD-like lung pathologies were measured. RESULTS: ADAM9 staining was increased in lung epithelial cells and macrophages in smokers and even more so in COPD patients and correlated directly with pack-year smoking history and inversely with airflow obstruction and/or FEV1 % predicted...
June 4, 2018: American Journal of Respiratory and Critical Care Medicine
Yibo Hua, Chao Liang, Chenkui Miao, Shangqian Wang, Shifeng Su, Pengfei Shao, Bianjiang Liu, Meiling Bao, Jundong Zhu, Aiming Xu, Jianzhong Zhang, Jie Li, Zengjun Wang
The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis...
June 2018: Oncology Letters
Jie Ding, Chiuan-Ren Yeh, Yin Sun, Changyi Lin, Joshua Chou, Zhenyu Ou, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression...
May 23, 2018: Oncogene
Kasper J Mygind, Theresa Störiko, Marie L Freiberg, Jacob Samsøe-Petersen, Jeanette Schwarz, Olav M Andersen, Marie Kveiborg
ADAM9 is an active member of the family of transmembrane ADAMs (a disintegrin and metalloproteases). It plays a role in processes such as bone formation and retinal neovascularization, and importantly, its expression in human cancers correlates with disease stage and poor prognosis. Functionally, ADAM9 can cleave several transmembrane proteins, thereby shedding their ectodomains from the cell surface. Moreover, ADAM9 regulates cell behavior by binding cell-surface receptors such as integrin and membrane-type matrix metalloproteases...
May 25, 2018: Journal of Biological Chemistry
Victor O Oria, Paul Lopatta, Oliver Schilling
A disintegrin and a metalloprotease (ADAM) 9 is a metzincin cell-surface protease involved in several biological processes such as myogenesis, fertilization, cell migration, inflammatory response, proliferation, and cell-cell interactions. ADAM9 has been found over-expressed in several solid tumors entities such as glioma, melanoma, prostate cancer, pancreatic ductal adenocarcinoma, gastric, breast, lung, and liver cancers. Immunohistochemical analyses highlight ADAM9 expression by actual cancer cells and associate its abundant presence with clinicopathological features such as shortened overall survival, poor tumor grade, de-differentiation, therapy resistance, and metastasis formation...
March 17, 2018: Cellular and Molecular Life Sciences: CMLS
Nuray Erin, Sema Türker, Özlem Elpek, Bülent Yildirim
ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time...
February 2018: Experimental and Therapeutic Medicine
Yinying Dong, Zhifeng Wu, Mingyan He, Yuhan Chen, Yixing Chen, Xiaoyun Shen, Xiaomei Zhao, Li Zhang, Baoying Yuan, Zhaochong Zeng
Interleukin (IL)-6 has been implicated in the invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular events that mediate this process are poorly understood. Here, we showed that IL-6 promoted the epithelial-mesenchymal transition (EMT) in HCC cell lines, and upregulated a disintegrin and metalloprotease 9 (ADAM9) expression by activating the JNK signaling pathway. ADAM9 was upregulated in human HCCs which promoted HCC cell invasion and the EMT by interacting with NADPH oxidase 1 and inducing reactive oxygen species generation...
May 1, 2018: Cancer Letters
Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Jer-Wei Chang, Kelly Su, Han-Shui Hsu, Shih-Chieh Hung
Epithelial-to-mesenchymal transition (EMT) is associated with tumor metastasis and tumorigenesis in lung cancer stem-like cells (CSCs). However, the exact mechanism underlying this is not clear. We used microarray analysis to identify candidate genes responsible for EMT in spheroid and monolayer cultures of lung cancer cells. We found increased expression of a variety of adhesion molecules in CSCs. One of these molecules, Collagen XVII (Col XVII), was demonstrated to be required for maintenance of EMT phenotypes and metastasis ability in lung CSCs...
January 5, 2018: Oncotarget
Pattaramon Tanasubsinn, Win Pa Pa Aung, Supansa Pata, Witida Laopajon, Anupong Makeudom, Thanapat Sastraruji, Watchara Kasinrerk, Suttichai Krisanaprakornkit
Overexpression of a disintegrin and metalloproteinase 9 (ADAM9) has been shown in various types of cancer. Some studies have reported inconclusive findings regarding chromosomal aberrations in the ADAM9 -containing region and ADAM9 expression in oral cancer. Therefore, in this study, ADAM9 protein expression was determined and compared between oral squamous cell carcinoma (OSCC) and normal oral tissues, and between oral cancer cell lines and human oral keratinocytes (HOKs). In total, 34 OSCC and 10 healthy paraffin-embedded tissue sections were probed with an anti-ADAM9 antibody, and the immunohistochemical score was determined by multiplying the percentage of positively stained cells with the intensity score...
January 2018: Oncology Letters
Mari Ueno, Takayuki Shiomi, Satsuki Mochizuki, Miyuki Chijiiwa, Masayuki Shimoda, Yae Kanai, Fumio Kataoka, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki, Yasunori Okada
ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in carcinomas than in control non-neoplastic ovarian tissue...
February 2018: Cancer Science
Marijn A Vermeulen, Shusma C Doebar, Carolien H M van Deurzen, John W M Martens, Paul J van Diest, Cathy B Moelans
Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis is challenging because of the rarity of this disease. We investigated copy number status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS) and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males using multiplex ligation-dependent probe amplification (MLPA). Results were compared to female BC and correlated with survival. Overall, copy number ratio and aberration frequency including all 22 genes showed no significant difference between the 3 groups...
March 2018: Endocrine-related Cancer
Chengwei Qin, Yanming Zhao, Chunzhi Gong, Zhenlin Yang
Breast cancer is the leading cause for cancer-associated mortality in women. Although great progress has been made in the earlier diagnosis and systemic therapy of patients with breast cancer in recent years, recurrence or distant metastasis continue to present major barriers to the successful treatment of breast cancer. Therefore, fully understanding the molecular mechanisms underlying the progression of breast cancer may be critical for the development of effective therapeutic strategies against breast cancer...
December 2017: Oncology Letters
Kasper J Mygind, Jeanette Schwarz, Pranshu Sahgal, Johanna Ivaska, Marie Kveiborg
The transmembrane protease ADAM9 is frequently upregulated in human cancers, and it promotes tumour progression in mice. In vitro , ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. However, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases β1 integrin levels through mechanisms that are independent of its protease activity. In ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins...
January 4, 2018: Journal of Cell Science
Dengdi Hu, Dan Shen, Min Zhang, Nengmeng Jiang, Feng Sun, Shibo Yuan, Kaiming Wan
MicroRNAs (miRNAs) have been identified as regulators of tumor proliferation, invasion, and metastasis in hepatocellular carcinoma (HCC). In the current study, we determined the clinical significance and biological role of miR-488 in HCC. Our results demonstrated that the expression of miR-488 was notably downregulated in HCC tissues compared with paired adjacent normal tissues. Lower miR-488 expression was positively associated with tumor size, vascular invasion, and shorter overall survival (OS) in HCC patients...
2017: American Journal of Cancer Research
Chen-Yuan Lin, Chia-Fong Cho, Shih-Ting Bai, Jing-Pei Liu, Ting-Ting Kuo, Li-Ju Wang, Yu-Sen Lin, Ching-Chan Lin, Liang-Chuan Lai, Tzu-Pin Lu, Chih-Ying Hsieh, Chin-Nan Chu, Da-Chuan Cheng, Yuh-Pyng Sher
Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo...
November 8, 2017: Scientific Reports
Deqiang Lei, Fangcheng Zhang, Dongxiao Yao, Nanxiang Xiong, Xiaobing Jiang, Hongyang Zhao
Galangin (3,5,7‑trihydroxyflavone), is a natural flavonoid present in plants. Galangin is reported to exhibit anti‑cancer properties against various cancer types. The aim of the present study was to display the effects of galangin on glioma and its mechanism of action in A172 human glioma cancer cells. The results clearly indicated that treatment of galangin inhibited A172 cell migration and invasion under non‑toxic doses. A human proteinase array assay was conducted to elucidate the potential effects of galangin, and the obtained results demonstrated that treatment of galangin inhibited ADAM9 protein expression and mRNA expression, that are known to contribute to cancer progression...
January 2018: Molecular Medicine Reports
Jun Arai, Kaku Goto, Anthony Stephanou, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Sayuri Morimoto, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato
BACKGROUND AND AIM: The multi-kinase inhibitor regorafenib (REG) was recently demonstrated to be effective in patients with sorafenib (SOR)-resistant hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA) in HCC cells and to block the production of soluble MICA (sMICA), an immunological decoy. In addition, MICA is associated with HCC in patients with chronic hepatitis C. We have now compared the impact of REG and SOR on MICA in HCC cells, as well as the immunotherapeutic implications thereof...
May 2018: Journal of Gastroenterology and Hepatology
Wanyue Huang, Ping Cheng, Kaiyuan Yu, Yanfei Han, Miao Song, Yanfei Li
Aluminum (Al) is a neurotoxicant and cause β-amyloid (Aβ) peptides aggregation and tau hyperphosphorylation. Hyperforin (HF) is one of the major active constituents of the extracts of St. John's Wort (Hypericum perforatum), can treat Alzheimer's disease (AD) and other diseases involving peptide accumulation and cognition impairment. To determine the effects of HF on Al-induced Aβ formation and tau hyperphosphorylation, PC12 cells were cultured and treated with Al-malt (500μM) and/or HF (1μM). The results showed that HF treatment significantly attenuated Al-malt-induced Aβ1-42 production by reducing the expressions of APP, BACE1 and PS1, while increasing the expressions of sAPPα, ADAM9/10/17, and tau phosphorylation in PC12 cells...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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