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https://www.readbyqxmd.com/read/29242607/the-impact-of-stromal-hic-5-on-the-tumorigenesis-of-colorectal-cancer-through-lysyl-oxidase-induction-and-stromal-remodeling
#1
Tomokatsu Omoto, Joo-Ri Kim-Kaneyama, Xiao-Feng Lei, Akira Orimo, Koji Ohnishi, Kosuke Yoshihara, Aya Miyauchi, Shuo Li, Lin Gao, Takahiro Umemoto, Junichi Tanaka, Kenta Nakahara, Motohiro Takeya, Fumio Ishida, Shin-Ei Kudo, Shogo Haraguchi, Takuro Miyazaki, Akira Miyazaki
Carcinoma-associated fibroblasts (CAFs) influence tumor initiation, progression, and metastasis within the tumor-associated stroma. This suggests that CAFs would be a potential target for tumor therapy. Here we found that Hydrogen peroxide-inducible clone-5 (Hic-5), also named transforming growth factor beta-1-induced transcript 1 protein (Tgfb1i1), was strongly induced in CAFs found in human colorectal cancer. To investigate the role of Hic-5 in CAFs, we isolated CAFs and the control counterpart normal fibroblasts (NFs) from human colorectal cancer and non-cancerous regions, respectively...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29229995/lysyl-oxidase-like-3-is-required-for-melanoma-cell-survival-by-maintaining-genomic-stability
#2
Patricia G Santamaría, Alfredo Floristán, Bárbara Fontanals-Cirera, Alberto Vázquez-Naharro, Vanesa Santos, Saleta Morales, Lourdes Yuste, Héctor Peinado, Antonio García-Gómez, Francisco Portillo, Eva Hernando, Amparo Cano
Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis. In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a significant upregulation of LOXL3 in human melanoma. We show that LOXL3 silencing impairs cell proliferation and triggers apoptosis in various melanoma cell lines. Further supporting a pro-oncogenic role in melanoma, LOXL3 favors tumor growth in vivo and cooperates with oncogenic BRAF in melanocyte transformation...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29225463/nano-copper-bearing-stainless-steel-promotes-fracture-healing-by-accelerating-the-callus-evolution-process
#3
Lei Wang, Guoyuan Li, Ling Ren, Xiangdong Kong, Yugang Wang, Xiuguo Han, Wenbo Jiang, Kerong Dai, Ke Yang, Yongqiang Hao
Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29215396/outcomes-of-corneal-cross-linking-correlate-with-cone-specific-lysyl-oxidase-expression-in-patients-with-keratoconus
#4
Rohit Shetty, Nimisha Rajiv Kumar, Natasha Pahuja, Rashmi Deshmukh, KrishnaPoojita Vunnava, Valsala Gopalakrishnan Abilash, Abhijit Sinha Roy, Arkasubhra Ghosh
PURPOSE: To evaluate the correlation of visual and keratometry outcomes after corneal cross-linking (CXL) in patients with keratoconus with cone epithelium-specific gene expression levels. METHODS: Corneal epithelium was obtained from 35 eyes that underwent accelerated CXL (KXLII, 9 mW/cm for 10 min). Using corneal topography, epithelium over the cone and periphery was obtained separately from each subject. The ratio of gene expression for lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), bone morphogenic protein 7, tissue inhibitor of metalloproteinase 1, collagen, type I, alpha 1, and collagen, type IV, alpha 1 (COL IVA1) from the cone and peripheral cornea was correlated with the outcome of cross-linking surgery...
December 5, 2017: Cornea
https://www.readbyqxmd.com/read/29209837/emerging-enzymatic-targets-controlling-angiogenesis-in-cancer-preclinical-evidence-and-potential-clinical-applications
#5
REVIEW
Biagio Ricciuti, Jennifer Foglietta, Rita Chiari, Amirhossein Sahebkar, Maciej Banach, Vanessa Bianconi, Matteo Pirro
Angiogenesis has always been considered as a fundamental therapeutic target for inhibiting tumor growth and metastasis. To date, anti-angiogenic treatments that have been approved are principally based on either administration of monoclonal antibodies targeting the vascular endothelial growth factor/vascular endothelial growth factor receptor axis or multikinase inhibitors. However, a growing body of evidence is pointing out the role of different classes of enzymes involved in tumor-driven angiogenesis, whose inhibition in preclinical models has already shown encouraging results...
December 4, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29209148/human-colorectal-cancer-progression-correlates-with-lox-induced-ecm-stiffening
#6
Bo Wei, Xueling Zhou, Chenghua Liang, Xiaoming Zheng, Purun Lei, Jiafeng Fang, Xiaoyan Han, Lijing Wang, Cuiling Qi, Hongbo Wei
Some solid tumors are characterized by extracellular matrix (ECM) remodeling and stiffening, which is related to solid tumor progression and aggression. However, the relationship between ECM stiffness and colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of ECM stiffness to clinicopathologic features using human CRC tissue microarrays. The results demonstrate that the expression of ECM components in CRC tissues is closely correlated with CRC progression and poor prognosis, which indicates that ECM stiffness may be associated with CRC development...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29207131/lysyl-oxidases-expression-and-histopathological-changes-of-the-diabetic-rat-nephron
#7
Jun Chen, Jie Ren, Wings T Y Loo, Liang Hao, Min Wang
Diabetic nephropathy (DN) is a major complication of diabetes, the accumulation of extracellular matrix (ECM) is considered an indication of nephropathological changes. Lysyl oxidases (LOXs) are also associated with ECM. However, the majority of studies on LOXs have focused on their potential role in renal fibrogenesis and there has no examination of LOXs expression or the correlation with histopathological changes of DN, including glomerular basement membrane (GBM) thickening and glomerulosclerosis. In this study, the association between histological changes and LOXs was explored using a type 2 diabetes model of male Zucker diabetic fatty rats...
November 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29201433/heart-regeneration-in-the-salamander-relies-on-macrophage-mediated-control-of-fibroblast-activation-and-the-extracellular-landscape
#8
J W Godwin, R Debuque, E Salimova, N A Rosenthal
In dramatic contrast to the poor repair outcomes for humans and rodent models such as mice, salamanders and some fish species are able to completely regenerate heart tissue following tissue injury, at any life stage. This capacity for complete cardiac repair provides a template for understanding the process of regeneration and for developing strategies to improve human cardiac repair outcomes. Using a cardiac cryo-injury model we show that heart regeneration is dependent on the innate immune system, as macrophage depletion during early time points post-injury results in regeneration failure...
2017: NPJ Regenerative Medicine
https://www.readbyqxmd.com/read/29184001/pace4-proteolytically-processes-loxl2-with-little-impact-on-its-catalytic-activity
#9
Kazushi Okada, Hee-Jung Moon, Joel Finney, Frédéric Couture, Robert Day, Minae Mure
Lysyl oxidase-like 2 (LOXL2) belongs to the LOX family of amine oxidases, which play a critical role in extracellular matrix remodeling by crosslinking collagen and elastin. Overexpression of LOX and/or LOXL2 drives fibrosis in several hepatic and vascular diseases, and tumor progression in some aggressive cancers. Because LOX and LOXL2 have a conserved Cterminal catalytic domain, LOXL2 is generally presumed to have the same biological activity as LOX. However, their N-termini are remarkably different and hint at potentially discrete functions and regulation...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29176937/proteomic-profiling-identifies-markers-for-inflammation-related-tumor-fibroblast-interaction
#10
Daniel Drev, Andrea Bileck, Zeynep N Erdem, Thomas Mohr, Gerald Timelthaler, Andrea Beer, Christopher Gerner, Brigitte Marian
Background: Cancer associated fibroblasts are activated in the tumor microenvironment and contribute to tumor progression, angiogenesis, extracellular matrix remodeling, and inflammation. Methods: To identify proteins characteristic for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass spectrometry to derive protein abundance from whole-tissue homogenates of human colorectal cancer/normal mucosa pairs. Alterations of protein levels were determined by two-sided t test with greater than threefold difference and an FDR of < 0...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/29167120/acute-lysyl-oxidase-inhibition-alters-microvascular-function-in-normotensive-but-not-hypertensive-men-and-women
#11
Daniel H Craighead, Huilei Wang, Lakshmi Santhanam, Lacy M Alexander
The Lysyl oxidase (LOX) family of enzymes regulates collagen cross-linking. LOX is upregulated in hypertension, increasing vascular stiffness. In vivo human research is sparse as long-term LOX inhibition in animals causes vascular instability. Our aim was to evaluate the effects of LOX inhibition on cutaneous microvascular function to determine if LOX function was upregulated in hypertensive humans. Four intradermal microdialysis fibers were placed in the forearm of 10 young (age: 24±1 y, MAP: 87±2 mmHg), 10 normotensive (age: 50±2 y, MAP: 84±1 mmHg), and 10 hypertensive (age: 53±2 y, MAP 112±2 mmHg) subjects...
November 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29165315/an-expression-screen-for-aged-dependent-micrornas-identifies-mir-30a-as-a-key-regulator-of-aging-features-in-human-epidermis
#12
Charlotte Muther, Lara Jobeili, Maëlle Garion, Sandrine Heraud, Amélie Thepot, Odile Damour, Jérôme Lamartine
The mechanisms affecting epidermal homeostasis during aging remain poorly understood. To identify age-related microRNAs, a class of non-coding RNAs known to play a key role in the regulation of epidermal homeostasis, an exhaustive miRNA expression screen was performed in human keratinocytes from young or elderly subjects. Many microRNAs modulated by aging were identified, including miR-30a, in which both strands were overexpressed in aged cells and epidermal tissue. Stable MiR-30a over-expression strongly impaired epidermal differentiation, inducing severe barrier function defects in an organotypic culture model...
November 19, 2017: Aging
https://www.readbyqxmd.com/read/29164236/posttranscriptional-regulation-of-loxl1-expression-via-alternative-splicing-and-nonsense-mediated-mrna-decay-as-an-adaptive-stress-response
#13
Daniel Berner, Matthias Zenkel, Francesca Pasutto, Ursula Hoja, Panah Liravi, Gabriele C Gusek-Schneider, Friedrich E Kruse, Johannes Schödel, Andre Reis, Ursula Schlötzer-Schrehardt
Purpose: Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors. Methods: Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29146187/lox-related-collagen-crosslink-changes-act-as-an-initiator-of-bone-fragility-in-a-zdf-rats-model
#14
Xun Xiao, Jie Ren, Jun Chen, Zhaohui Liu, Ye Tian, Neel R Nabar, Min Wang, Liang Hao
Diabetes mellitus type 2 (DM2) results in bone abnormalities that manifest as increased bone fragility. Bone consists of two phases, the mineral phase and the matrix phase, and disorders in both are seen in DM2. However, the phase in which DM2 mediated bone fragility is initiated is still unknown. In this study, a male Zucker diabetic fatty (fa/fa) (ZDF) rat model was used to investigate the underlying mechanism initiating DM2 mediated bone fragility. The fracture surface morphology, pre- and post-yield bone mechanical behavior, insoluble collagen volume, lysyl oxidase family (LOX) enzyme levels and correlation analysis was performed to determine the relationship between insoluble collagen and post-yield behavior...
November 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29135319/crosslinking-enzyme-lysyl-oxidase-modulates-scleral-remodeling-in-form-deprivation-myopia
#15
Ying Yuan, Min Li, Qingzhong Chen, Rao Me, Yunjie Yu, Qing Gu, Guangsen Shi, Bilian Ke
PURPOSE: Scleral remodeling causes the excessive ocular elongation that underlies myopia. Lysyl oxidase (LOX), a copper-containing amine oxidase, can catalyze collagen and elastin crosslinking. The purpose of this study was to investigate the role of LOX in scleral remodeling in form-deprivation myopia (FDM). METHODS: Seventy-five guinea pigs were randomly divided into five groups as follows: a normal control group, an FDM group, an FDM plus β-aminopropionitrile (BAPN) group, an FDM plus TGF-β1 (TGF-β1) group, and an FDM plus vehicle group...
November 14, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29130678/-expression-of-lox-in-colorectal-cancer-tissues-and-its-relationship-with-progress-and-prognosis
#16
Xiao-Ming Shi, Wei Zhao, Yong-Bin Yang, Bo-Nan Lü
OBJECTIVE: To analyze the expression of lysyl oxidase (LOX) in colorectal cancer and its relationship with clinicopathological characteristics, prognosis, and its progress. METHODS: 82 cases of colorectal tumor paraffin-embedded specimens and paired tumor-adjacent tissues were collected, and data of clinicopathological characteristics and prognosis of these patients were also recorded from 2009.1 to 2010.5. Expressions of LOX, hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7 were determined by immunohistochemistry...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29127553/identification-of-histidine-303-as-the-catalytic-base-of-lysyl-oxidase-via-site-directed-mutagenesis
#17
Rachel N Oldfield, Kathryn A Johnston, Jeanette Limones, Caitlin Ghilarducci, Karlo M Lopez
Lysyl oxidase (LOX) is a copper-dependent amine oxidase enzyme that catalyzes the formation of crosslinkages of collagen and elastin in connective tissues by oxidative deamination of lysine. Using site-directed mutagenesis, Histidine 303 has been shown to be a key residue that acts as the necessary catalytic base for this enzyme to function properly. Histidine 303 was mutated to isoleucine to remove catalytic activity and to aspartate and glutamate, respectively, in order to provide alternate residues that could act as a general base that could maintain catalytic activity...
November 10, 2017: Protein Journal
https://www.readbyqxmd.com/read/29125826/lysyl-oxidases-regulate-fibrillar-collagen-remodelling-in-idiopathic-pulmonary-fibrosis
#18
Gavin Tjin, Eric S White, Alen Faiz, Delphine Sicard, Daniel J Tschumperlin, Annabelle Mahar, Eleanor P W Kable, Janette K Burgess
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with few effective therapeutic options. Structural remodelling of the extracellular matrix [i.e. collagen cross-linking mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4)] might contribute to disease pathogenesis and represent a therapeutic target. This study aimed to further our understanding of the mechanisms by which LO inhibitors might improve lung fibrosis. Lung tissues from IPF and non-IPF subjects were examined for collagen structure (second harmonic generation imaging) and LO gene (microarray analysis) and protein (immunohistochemistry and western blotting) levels...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29115860/lysyl-oxidase-like-1-protein-deficiency-protects-mice-from-adtgf-%C3%AE-1-induced-pulmonary-fibrosis
#19
Pierre-Simon Bellaye, Chiko Shimbori, Chandak Upagupta, Seidai Sato, Wei Shi, Jack Gauldie, Kjetil Ask, Martin Kolb
Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue disturbing gas-exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of TGF-β1, one of the main pro-fibrotic growth factors. Lysyl oxidase-like1 (LOXL1) belongs to the crosslinking enzyme family and has been shown to be upregulated in active fibrotic regions of bleomycin-treated mice and IPF patients...
November 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29113306/role-of-loxl2-in-the-epithelial-mesenchymal-transition-and-colorectal-cancer-metastasis
#20
Pil-Gu Park, Su Ji Jo, Min Jung Kim, Hyun Jeong Kim, Ji Hae Lee, Cheol Keun Park, Hyunki Kim, Kang Young Lee, Hoguen Kim, Jeon Han Park, Seung Myung Dong, Jae Myun Lee
Colorectal cancer (CRC) is one of the most dangerous types of malignant tumors, and cancer metastasis is a major factor in the failure of CRC therapy. Recently, LOXL2 (lysyl oxidase-like 2) has been shown to represent a regulator of epithelial-mesenchymal transition (EMT) in different cancer types. However, LOXL2 has not been reported to be involved in CRC metastasis. In this study, we demonstrated that LOXL2 expression is strongly correlated with the rate of CRC metastasis, it participates in the regulation of EMT-related molecule expression in CRC cells in vitro, and it is involved in migratory potential alterations...
October 6, 2017: Oncotarget
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