A disintegrin and metalloproteinase domain-containing protein 10 (ADAM-10) involves in the tumour progression, but the impacts of single-nucleotide polymorphism (SNP) of ADAM-10 on oral squamous cell carcinoma (OSCC) remain unclear. The aim of this study was to investigate the influence of SNP of ADAM-10 on the clinical features of OSCC in male Taiwanese. Five loci of ADAM-10 SNPs including rs653765 (C/T), rs2305421 (A/G), rs514049 (A/C), rs383902 (T/C) and rs2054096 (A/T) were genotyped by TaqMan allelic discrimination in 1138 OSCC patients and 1199 non-OSCC individuals. The ADAM-10 SNP rs2305421 GG (AOR: 1.399, 95% CI: 1.045-1.874, p = 0.024) and G allele (AOR: 1.170, 95% CI: 1.012-1.351, p = 0.034) illustrated a significantly higher genotypic frequencies in the OSCC group compared to the distribution of the ADAM-10 SNP rs2305421 AA wild type. In the subgroup analysis, the ADAM-10 SNP rs383902 TC+CC was significantly correlated to tumour size larger than T2 in betel quid chewer (AOR: 1.375, 95% CI: 1.010-1.872, p = 0.043), while the ADAM-10 SNP rs653765 CT+TT was significantly associated with tumour size larger than T2 in cigarette smoker (AOR: 1.346, 95% CI: 1.023-1.772, p = 0.034). The results from The Cancer Genome Atlas revealed highest ADAM-10 mRNA level in T2 stage of current smokers with head and neck squamous cell carcinoma (HNSCC). In conclusions, the ADAM-10 SNP rs2305421 G allele is associated with the presence of OSCC, and the ADAM-10 SNP rs383902 TC+CC and ADAM-10 SNP rs653765 CT+TT correlates to large tumour size in specific conditions.

Growth arrest-specific protein 6 (GAS-6) regulates immunomodulatory and inflammatory mechanisms in periodontium and may participate in obesity predisposition. This study aimed to determine whether GAS-6 is associated with the homeostasis of periodontal ligament (SV-PDL) cells in the presence of adipokines or compressive forces. The SV-PDL cell line was used. Western blots were employed for TAM receptors detection. Cells were stimulated using different concentrations of GAS-6. The migration, viability, and proliferation were measured by a standard scratch test, MTS assay, and immunofluorescent staining. The mRNA expression was analyzed by RT-PCR. Release of TGF-β1, GAS-6, and Axl were verified by ELISA. Western blot shows that TAM receptors are expressed in SV-PDL cells. GAS-6 has a promoting effect on cell migration and proliferation. RT-PCR analysis showed that GAS-6 induces Collagen-1, Collagen-3, Periostin, and TGF-β1 mRNA expression whereas it reduces Caspase-3, Caspase-8, Caspase-9, and IL-6 mRNA expression. Further, secreted GAS-6 in SV-PDL is reduced in response to both compressive forces and leptin and upregulated by IL-6. Additionally, ADAM-10 inhibition reduces GAS-6 and Axl release on SV-PDL cells. TAM receptors especially Axl are identified as the receptors of GAS-6. GAS-6/TAM interactions contribute to periodontal ligament cells homeostasis. Leptin inhibits the GAS-6 release independently of ADAM-10 metalloprotease.

Cellular prion protein (PrPC) is a lipid raft protein abundant within CNS. It is regulated by a disintegrin and metalloproteinase domain containing protein 10 (ADAM10). PrPC has previously been implicated as a biomarker for TBI. ADAM10 has not been investigated as a TBI biomarker.
We evaluated PrPC and ADAM10 as candidate biomarkers for TBI.
We performed ELISA for ADAM10 and PrPC on plasma samples of patients with TBI admitted to Brigham and Women\'s Hospital. Plasma samples from 20 patients admitted for isolated TBI were acquired from a biobank with clinical information. Control plasma (37 samples) was acquired from a commercial source. GraphPad was used to conduct statistical analysis.
37 controls and 20 TBI samples were collected. Of the patients with TBI, eight were mild, three were moderate, and nine were severe. Both PrPC and ADAM10 were elevated in patients with TBI compared with control (p < .001). ADAM10 exhibited greater expression in patients with worse clinical grade. There was no significant association of either PrPC or ADAM10 with time after injury.
Our results indicate that PrPC and ADAM10 appear to be useful potential tools for screening of TBI. ADAM10 is closely associated with clinical grade.

Background: As is known, exosomes play an important role in promoting progression of cancers by increasing its invasive potential. The aim of this study was to evaluate the levels of tetraspanine-associated (ADAM-10) and tetraspanine-nonassociated proteases (20S proteasomes) in exosomes from culture medium, plasma exosomes of patients with breast tumors and plasma and ascites of ovarian tumor patients. Methods: MCF-7 and SVO-3 culture mediums and blood samples from healthy females (n = 30, HFs), patients with diffuse dyshormonal dysplasia of the breast (n=28, BBTPs), breast cancer patients (n=32, BCPs), borderline ovarian tumor patients (n=20, BOTPs) and blood and ascites samples ovarian cancer patients (n=35, OCPs) were included in the study. Exosomes from plasma, ascites and culture mediums were isolated and characterized in according to Extracellular Vesicles Society. The expression levels of 20S proteasome and ADAM-10 in exosomes were determined using flow cytometry and western blot analysis, correspondingly. Results: The subpopulation composition of the exosomes from MCF-7 culture medium and from blood plasma of HFs and breast diseases patients is similar, however CD9/CD24 subpopulation significantly increased at cell supernatant. The similar results was obtained for exosomes from SVO-3 medium and blood plasma and ascites of ovary tumor patients, but CD9/CD24 subpopulation significantly decreased at cells and illness samples, however CD63/CD24 exosomes increased significantly from cell supernatant. 20S proteasome level is significantly increased in exosomes from MCF-7 and SVO-3 culture medium, breast tumor patients and OCPs plasma in comparison to HUVEC culture medium and HFs plasma samples. At CD9-positive exosomes from BCPs plasma and MCF-7 was reveal a high expression of ADAM-10 and low expression is from BBDPs plasma and ovarian tumor patients plasma/ ascites samples. Exosomes from ascites OCP had high expression of ADAM-10 in the CD24-positive subpopulation. Conclusion: Breast and ovarian cancer development is connected with functioning of immune proteasome forms in plasma and ascites exosomes, while increased ADAM10 expression at CD9-positive exosome was associated with breast cancer and at CD24-positive subpopulation – with ovarian cancer. Obtained data confirm role of exosomal proteases in tumor progression.

OBJECTIVE: A disintegrin and metalloproteinase (ADAM)-10 is expressed in rheumatoid arthritis (RA). In this study, we focused on ADAM-10 as a predictive factor for the treatment with biologics in RA.
METHODS: The levels of ADAM-10 and fractalkine/CX3CL1 in RA and healthy controls serum were measured using enzyme-linked immunosorbent assays. Fifteen patients were treated with adalimumab (ADA), and 20 patients were treated with tocilizumab (TCZ).
RESULTS: ADAM-10 positively correlated with fractalkine/CX3CL1 in the sera of RA patients and was presented at a significantly higher level compared to that in normal serum (487 ± 80 pg/ml and 85 ± 33 pg/ml, respectively, p < 0.05). ADAM-10 highly correlates with fractalkine/CX3CL1 in the sera of RA patients. The level of ADAM-10 decreased after the treatment with TCZ but not with ADA. In addition, we found that the level of ADAM-10 in TCZ responders was significantly higher than that of the TCZ nonresponders at 24 weeks (619 ± 134 pg/ml and 109 ± 25 pg/ml, respectively). Multiple regression analysis showed that ADAM-10 was only identified as independent predictive variable for the improvement of DAS28 (ESR) at 24 weeks.
CONCLUSIONS: ADAM-10 may be a predictor of the effectiveness of TCZ in treating RA.

Although excessive mechanical stress loading is known to induce articular cartilage degradation, the mechanism underlying this process is unclear. The interaction between hyaluronan (HA) and its primary receptor CD44 maintains the homeostasis of articular chondrocytes. CD44 cleavage and the generation of CD44-intracellular domain (ICD) can lead to the loss of extracellular matrices in chondrocytes. Here we studied the effects of cyclic tensile strain (CTS) loading, a representative mechanical stress, on CD44 cleavage. CTS loading (1 Hz and 20% elongation for 48 h) increased ADAM10 expression and CD44 cleavage in HCS-2/8 cells, a human chondrocytic cell line. Co-treatment with a chemical ADAM10 inhibitor significantly suppressed CTS loading-induced CD44 cleavage. Chemical inhibition of transient receptor potential vanilloid 4 (TRPV4) significantly suppressed CTS loading-induced ADAM10 expression and CD44 cleavage. Conversely, chemical activation of TRPV4 increased ADAM10 expression and enhanced CD44 cleavage. Our findings suggest that CTS loading significantly increases the expression of ADAM10, which in turn enhances CD44 cleavage in HCS-2/8 cells. The primary mechanoreceptor mediating this process is TRPV4. This signature event could provide an avenue for intervention in the prevention of cartilage degradation leading to OA.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in humans, whose invasiveness and proliferation are associated with poor prognosis. Matrix metalloproteinases (MMPs) and the related family of \"a disintegrin and metalloproteinase\" (ADAM) both contribute to increase cell invasion, and its substrate N-cadherin is involved in proliferation and metastatic capacities of tumor cells. However, these molecular determinants of aggressiveness have not been adequately characterized in GBM. In an attempt to better define these pathogenetic signatures, in the present study we evaluated the comparative expression of two main MMPs (MMP-2 and -9), as well as of ADAM-10 and N-cadherin in surgical samples from patients diagnosed with WHO grade IV GBM (n = 25) and in cortical tissue specimens obtained from untreatable epileptic patients (controls, n = 8) through a series of histopathological, immunohistochemical and biochemical tests. Our studies revealed that both MMP-2 and -9 immunoreactivities (IRs) were upregulated in 13 of 25 (52 %) and 19 of 25 (76 %) GBMs, respectively, and the extent of the increase was highly significant with respect to controls (p < 0.001). ADAM-10 IR was also found to be increased (p < 0.001) in 16 of 25 GBM specimens (64 %). Conversely, N-cadherin IR was remarkably decreased (p < 0.001) in almost the totality of tumor samples (22 of 25, 88 %). A similar trend was also obtained at the mRNA and protein level by qPCR and western blot analyses, respectively. Collectively, the current study provides a comprehensive molecular portrayal of some of the major pathological hallmarks of GBM aggressiveness, which could be exploitable as potential targets for a new therapeutic approach.

Atherosclerosis remains a major cause of mortality. Whereas the histopathological progression of atherosclerotic lesions is well documented, much less is known about the development of unstable or vulnerable plaque, which can rupture leading to thrombus, luminal occlusion and infarct. Apoptosis in the fibrous cap, which is rich in vascular smooth muscle cells (VSMCs) and macrophages, and its subsequent weakening or erosion seems to be an important regulator of plaque stability. The aim of our study was to improve our knowledge on the biological mechanisms that cause plaque instability in order to develop new therapies to maintain atherosclerotic plaque stability and avoid its rupture. In our study, we collected surgical specimens from atherosclerotic plaques in the right or left internal carotid artery of 62 patients with evident clinical symptoms. Histopathology and histochemistry were performed on wax-embedded sections. Immunohistochemical localization of caspase-3, N-cadherin and ADAM-10 was undertaken in order to highlight links between apoptosis, as expressed by caspase-3 immunostaining, and possible roles of N-cadherin, a cell-cell junction protein in VSMCs and macrophages that provides a pro-survival signal reducing apoptosis, and ADAM-10, a \"disintegrin and metalloproteases\" that is able to cleave N-cadherin in glioblastomas. Our results showed that when apoptosis, expressed by caspase-3 immunostaining, increased in the fibrous cap, rich in VSMCs and macrophages, the expression of N-cadherin decreased. The decreased N-cadherin expression, in turn, was linked to increased ADAM-10 expression. This study shows that apoptotic events are probably involved in the vulnerability of atherosclerotic plaque.

A Disintegrin and Metalloproteinase (ADAM)-10 plays critical roles in neuronal migration and distribution. Recently, ADAM10 deletion was shown to disrupt myelopoiesis. We found that inducible deletion of ADAM10 using Mx1-driven Cre recombinase for a period of three weeks resulted in mast cell hyperplasia in the skin, intestine and spleen. Mast cells express surface ADAM10 in vitro and in vivo, at high levels compared to other immune cells tested. ADAM10 is important for mast cell migration, since ADAM10-deficiency reduced c-Kit-mediated migration. As with some mast cell proteases, ADAM10 expression could be altered by the cytokine microenvironment, being inhibited by IL-10 or TGFβ1, but not by several other T cell-derived cytokines. Collectively these data show that the ADAM10 protease is an important factor in mast cell migration and tissue distribution, and can be manipulated by environmental cues.

Inhibition of Aβ production and clearance of senile plaques have been considered as potential strategies in the treatment of Alzheimer\'s disease (AD). Activated protein C (APC) is an important factor in the anticoagulant system. However, whether APC can influence the condition of a chronic neurodegenerative process, such as that present in AD, is unknown. In this study, we found that administration of APC on AD Tg2576 mice significantly reduced amyloid β production and helped to facilitate cognitive improvement. APC could also reduce levels of Aβ40 and Aβ42 produced in APPswe cells, an AD cell model. Further results demonstrated that APC did not change the levels of Aβ-degrading enzymes, insulin-degrading enzyme (IDE), or neprilysin (NEP). Next, we found that APC promoted sAPPα and CTFα release and inhibited sAPPβ and CTFβ release, thereby indicating that APC could regulate Aβ secretion by shifting APP processing from the amyloidogenic pathway toward the nonamyloidogenic pathway. Correspondingly, further study revealed that ADAM-10 expression was increased by APC, suggesting that APC inhibits Aβ secretion through stimulating activity of α-secretase. These findings support the idea that APC could hold therapeutic potential in the treatment of AD.