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Elmina Mammadova-Bach, Paola Zigrino, Camille Brucker, Catherine Bourdon, Monique Freund, Adèle De Arcangelis, Scott I Abrams, Gertaud Orend, Christian Gachet, Pierre Henri Mangin
Metastatic dissemination of cancer cells, which accounts for 90% of cancer mortality, is the ultimate hallmark of malignancy. Growing evidence suggests that blood platelets have a predominant role in tumor metastasis; however, the molecular mechanisms involved remain elusive. Here, we demonstrate that genetic deficiency of integrin α6β1 on platelets markedly decreases experimental and spontaneous lung metastasis. In vitro and in vivo assays reveal that human and mouse platelet α6β1 supports platelet adhesion to various types of cancer cells...
September 8, 2016: JCI Insight
Nuray Erin, Tümay İpekçi, Bahar Akkaya, İrem Hicran Özbudak, Mehmet Baykara
BACKGROUND: ADAM9, 10, and 17 are a class of disintegrins and metallproteinases with α-secretase activity. There are conflicting results regarding the role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have examined their levels and cellular localization in renal cell carcinoma (RCC). Studies examining changes in α-secretase activity in RCC compared to enzymatic activity of the uninvolved kidney are lacking. METHOD: A cross-sectional study was conducted in 56 patients undergoing radical nephrectomy after the diagnosis of RCC...
September 28, 2016: Urologic Oncology
Tian Tian, Dong Bai, Wen Li, Guo-Wei Huang, Huan Liu
Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase...
2016: Nutrients
Xing Fan, Yongheng Wang, Chuanbao Zhang, Li Liu, Sen Yang, Yinyan Wang, Xing Liu, Zenghui Qian, Shengyu Fang, Hui Qiao, Tao Jiang
The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas...
2016: International Journal of Molecular Sciences
Kelli Cristina Micocci, Milene Nóbrega de Oliveira Moritz, Rafael Luis Bressani Lino, Laila Ribeiro Fernandes, Antonio Gilclêr Ferreira Lima, Camila Castro Figueiredo, Verônica Morandi, Heloisa Sobreiro Selistre-de-Araujo
ADAMs are transmembrane multifunctional proteins that contain disintegrin and metalloprotease domains. ADAMs act in a diverse set of biological processes, including fertilization, inflammatory responses, myogenesis, cell migration, cell proliferation and ectodomain cleavage of membrane proteins. These proteins also have additional functions in pathological processes as cancer and metastasis development. ADAM9 is a member of ADAM protein family that is overexpressed in several types of human carcinomas. The aim of this study was to investigate the role of ADAM9 in hematogenous and lymphatic tumor cell dissemination assisting the development of new therapeutic tools...
September 2016: Biochimie
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...
August 11, 2016: Oncotarget
Laura R A Schouten, Hendrik J F Helmerhorst, Gerry T M Wagenaar, Tom Haltenhof, René Lutter, Joris J T H Roelofs, Job B M van Woensel, Anton H L C van Kaam, Albert P Bos, Marcus J Schultz, Thomas Walther, Roelie M Wösten-van Asperen
OBJECTIVES: A growing body of evidence suggests that age affects the main pathophysiologic mechanisms of the acute respiratory distress syndrome. This may imply the need for developing age-tailored therapies for acute respiratory distress syndrome. However, underlying molecular mechanisms governing age-related susceptibility first need to be unraveled. In a rat model of acute lung injury, we investigated whether age affects the balance between the two key enzymes of the pulmonary renin-angiotensin system, angiotensin-converting enzyme, and angiotensin-converting enzyme 2...
August 10, 2016: Critical Care Medicine
Xiaogang Liu, Shanjun Wang, Aiqin Yuan, Xunhui Yuan, Bing Liu
Glioma is the most frequent primary malignant tumor of the human brain. Recently, great progress has been made in the combined therapy of glioma. However, the clinical effects of these treatments and prognosis for patients with glioma remains poor. MicroRNAs (miRNAs) have been demonstrated to play important roles in the initiation and progression of various types of human cancers, also including glioma. The present study investigated the expression patterns of microRNA‑140 (miR-140) in glioma, and the roles of miR-140 in glioma cell proliferation, migration and invasion...
October 2016: Oncology Reports
Y-Q Wang, D-H Qu, K Wang
Amyloid beta (Aβ) plaques are pathological hallmarks of neurodegenerative Alzheimer's disease (AD) that is predominantly characterized by clinical symptoms of dementia. Therapies targeting Aβ are essential for preventing and treating AD. This review focuses on the non-amyloidogenic pathways that prevent the generation of Aβ peptide and thereby plaque formation in AD. An a-secretase-dependent cleavage of Amyloid Precursor Protein (APP) precludes the amyloidogenic pathway of Aβ generation. This non-amyloidogenic a-secretase activation thereby secretes sAPPa with prominent neurotrophic and memory-enhancing properties...
June 2016: European Review for Medical and Pharmacological Sciences
Wing Yip Tam, Ngan Pan Bennett Au, Chi Him Eddie Ma
Microglia are immune cells in the central nervous system (CNS) that contribute to primary innate immune responses. The morphology of microglia is closely associated with their functional activities. The majority of microglial studies have focused on the ramified or amoeboid morphology; however, bipolar/rod-shaped microglia have recently received much attention. Bipolar/rod-shaped microglia form trains with end-to-end alignment in injured brains and retinae, which is proposed as an important mechanism in CNS repair...
2016: Scientific Reports
Marcia L Moss, Dmitriy Minond, Toshie Yoneyama, Hinrich P Hansen, Nikola Vujanovic, Fred H Rasmussen
A fluorescent resonance energy transfer substrate with improved sensitivity for ADAM17, -10, and -9 (where ADAM represents a disintegrin and metalloproteinase) has been designed. The new substrate, Dabcyl-Pro-Arg-Ala-Ala-Ala-Homophe-Thr-Ser-Pro-Lys(FAM)-NH2, has specificity constants of 6.3 (±0.3) × 10(4) M(-1) s(-1) and 2.4 (±0.3) × 10(3) M(-1) s(-1) for ADAM17 and ADAM10, respectively. The substrate is more sensitive than widely used peptides based on the precursor tumor necrosis factor-alpha (TNF-alpha) cleavage site, PEPDAB010 or Dabcyl-Ser-Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Lys(FAM)-NH2 and Mca-Pro-Leu-Ala-Gln-Ala-Val-Dpa-Arg-Ser-Ser-Arg-NH2...
August 15, 2016: Analytical Biochemistry
Xin Liu, Hua Duan, Heng-Hui Zhang, Lu Gan, Qian Xu
BACKGROUND: Adhesion tissue is formed following injury to the uterine basal layer. Currently, there is no effective treatment for severe intrauterine adhesion (IUA), which causes loss of reproductive function. Enhanced understanding of the molecular mechanisms driving severe IUA would be beneficial for the treatment. METHODS: Differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in severe IUA (n = 3) and normal (n = 3) endometrium were analyzed by high-throughput microarray analysis...
October 2016: Reproductive Sciences
T Kauttu, H Mustonen, S Vainionpää, L Krogerus, I Ilonen, J Räsänen, J Salo, P Puolakkainen
BACKGROUND: Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry...
March 30, 2016: Clinical & Translational Oncology
Mei-Chi Chang, Chiu-Po Chan, Yi-Jane Chen, Hsiang-Chi Hsien, Ya-Ching Chang, Sin-Yuet Yeung, Po-Yuan Jeng, Ru-Hsiu Cheng, Liang-Jiunn Hahn, Jiiang-Huei Jeng
Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production...
March 29, 2016: Oncotarget
Qian Zhang, Wenyu Gou, Xiaotong Wang, Yawen Zhang, Jun Ma, Hongliang Zhang, Ying Zhang, Hao Zhang
Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation...
March 2016: Genome Biology and Evolution
Liang Chang, Fangchao Gong, Hongfei Cai, Zhihong Li, Youbin Cui
Previous studies have demonstrated that human signal transducer and activator of transcription 3 (Stat3) and disintegrin and metalloproteinase 9 (ADAM9) are promising targets for RNA interference (RNAi)-based gene therapy for human non-small cell lung cancer (NSCLC). Thus, in the present study, the recombinant lentiviral (Lv) small hairpin (sh)RNA expression plasmids Lv/sh-Stat3 and Lv/sh-ADAM9, which targeted Stat3 and ADAM9, respectively, were constructed and subsequently infected into the A549 human NSCLC cell line...
February 2016: Oncology Letters
Dorothee Kaudewitz, Philipp Skroblin, Lukas H Bender, Temo Barwari, Peter Willeit, Raimund Pechlaner, Nicholas P Sunderland, Karin Willeit, Allison C Morton, Paul C Armstrong, Melissa V Chan, Ruifang Lu, Xiaoke Yin, Filipe Gracio, Katarzyna Dudek, Sarah R Langley, Anna Zampetaki, Emanuele de Rinaldis, Shu Ye, Timothy D Warner, Alka Saxena, Stefan Kiechl, Robert F Storey, Manuel Mayr
RATIONALE: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with platelet function. OBJECTIVE: To link small RNAs to platelet reactivity. METHODS AND RESULTS: Next-generation sequencing of small RNAs in plasma revealed 2 peaks at 22 to 23 and 32 to 33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly, fragments of RNY4 and RNY5 were detected...
February 5, 2016: Circulation Research
Bin Shen, Yongxiang Wang, Xiang Wang, Yifeng Du, Shougang Guo, Lin Cong
PURPOSE OF THE STUDY: To investigate the induction of 'a disintegrin and metalloprotease' 9 (ADAM9) by which estrogen receptor (ER) subtypes and estrogen regulation of expression in cultured human neuronal cells. METHODS: SH-SY5Y cells were treated with E2 and the expression of ADAM9 were detected by RT-PCR and Western blot analysis. The peGFP-C3-ERα and peGFP-C3-ERβ vectors were constructed and transfected into SH-SY5Y cells. Then, the mRNA and protein expression level of ADAM9 were detected by RT-PCR and Western blot analyses with the treatment of E2...
February 1, 2016: Gene
Kuo-Liang Chiu, Ting-Ting Kuo, Qian-Yu Kuok, Yu-Sen Lin, Chung-Hung Hua, Chen-Yuan Lin, Pei-Yuan Su, Liang-Chuan Lai, Yuh-Pyng Sher
Metastasis is the leading cause of death in cancer patients due to the difficulty of controlling this complex process. MicroRNAs (miRNA), endogenous noncoding short RNAs with important biological and pathological functions, may play a regulatory role during cancer metastasis, but this role has yet to be fully defined. We previously demonstrated that ADAM9 enhanced the expression of the pro-migratory protein CDCP1 to promote lung metastasis; however, the regulatory process remains unknown. Here we demonstrate that endogenous miR-218, which is abundant in normal lung tissue but suppressed in lung tumors, is regulated during the process of ADAM9-mediated CDCP1 expression...
2015: Scientific Reports
Chuankai Zhang, Yunda Zhang, Weiji Ding, Yancheng Lin, Zhengjie Huang, Qi Luo
MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells...
December 2015: Protein & Cell
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