Urinary ADAM12 and MMP-9/NGAL Complex Detect the Presence of Gastric Cancer

Shimura, Takaya; Dagher, Adelle; Sachdev, Monisha; Ebi, Masahide; Yamada, Tamaki; Yamada, Terumasa; Joh, Takashi; Moses, Marsha A.

doi:10.1158/1940-6207.capr-14-0229

Cited by 48 publications

(44 citation statements)

References 52 publications

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“…Moreover, MMP-9 levels were found to be significantly higher in the serum of gastric cancer patients when compared with those of controls [54]. Evaluation of urine samples from individuals with gastric cancer versus healthy controls also revealed that urinary MMP-9/NGAL complex was a potential biomarker of early-stage gastric cancer [57]. In addition, a number of meta-analyses found that overexpression of MMPs was associated with poor prognosis in gastric cancer patients, as was the case for MMP-9 and MMP-2 [50,51,56].…”

Section: Col6a3mentioning

confidence: 91%

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Moreira

Pereira

Melo

et al. 2020

Cells

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The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.

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Section: Col6a3mentioning

confidence: 91%

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Moreira

Pereira

Melo

et al. 2020

Cells

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“…For example, gene-targeting strategies in mice indicate ADAM12 as a key regulator in myogenesis 12 and adipogenesis, 13 while in vitro studies have assigned roles for ADAM12 in promoting cell fusion in osteoclasts 14 and trophoblasts. 15 ADAM12 also positively associates, and in some cases promotes, the progression of chronic disease states including multiple subtypes of cancer, [16][17][18] fibrosis, 19 and cardiac hypertrophy. 20 The secreted variant, ADAM12S, strongly links with cancer progression where serum levels are elevated in patients with highly-invasive metastatic breast cancer, while ADAM12S over-expression promotes breast cancer cell invasion.…”

Section: Diverse Proteases Coordinate Invasive Trophoblast Biologymentioning

confidence: 99%

ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts

Christians

Beristain

2016

Cell Adhesion & Migration

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Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have been consistently associated with the subsequent development of preeclampsia and fetal growth restriction. These molecules are both metalloproteinases secreted by the placenta that cleave insulin-like growth factor binding proteins (IGFBPs), although ADAM12 also has numerous other substrates. Recent work has identified ADAM12, and particularly its shorter variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts into the lining of the uterus, a critical step in normal placental development. While the mechanisms underlying this regulation are not yet clear, they may involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or IGFs from IGFBPs. In contrast, there has been relatively little functional work examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the functions of these markers and the mechanisms underlying their association with disease could improve screening strategies and enable the development of new therapeutic interventions.

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“…Indeed, the putative substrates of ADAM9, ADAM10 and ADAM17 identified by MS in CSF fluid, according to MEROPS, include amyloid beta A4 protein (Table S1, Supporting Information), supporting its involvement in AD pathogenesis. These ADAM proteases were already assessed in body fluids, mostly in blood‐derived ones, with ELISA approaches, and related with other pathological conditions besides AD …”

Section: Comparative Analysis Of Proteases Distribution Among Distincmentioning

confidence: 99%

Reviewing Mechanistic Peptidomics in Body Fluids Focusing on Proteases

et al. 2018

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The comprehension of how protease networks sculpt proteomes might help to disclose the functional annotation of the peptidome in health and disease. Envisioning to add new insights on the protease networks involved in the regulation of body fluid peptidomes, the authors apply Proteasix software to predict the proteases involved in the generation of the naturally occurring peptides present in six of the most studied human body fluids. Peptidome data is collected from the databases and from experimental studies. The analysis highlights 132 putative proteases from four families with the predominance of serine proteases and metalloproteases. From these, 49 proteases seem to be common to all fluids and are mostly associated to extracellular matrix organization as well as protein/peptide hormone processing. Data analysis also emphasizes: i) the similarity between plasma and CSF protease profiles; ii) that saliva and tears share proteases involved in the generation of peptides with antimicrobial activity; iii) that urine is the body fluid with the highest number of unique putative proteases, precluding an easy tracing of proteolytic events in this case. Taken together, the analysis emphasizes the intricate modus operandi of proteases, challenged by the interconnected pathways and amplification cascades in which they are involved.

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Urinary ADAM12 and MMP-9/NGAL Complex Detect the Presence of Gastric Cancer

Cited by 48 publications

References 52 publications

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts

Reviewing Mechanistic Peptidomics in Body Fluids Focusing on Proteases

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