Matrix metalloproteinases, inhibitor of metalloproteinases mRNA and protein expression in laryngeal squamous cell carcinoma

Grzelczyk, Weronika Lucas; Wróbel-Roztropiński, Artur; Szemraj, Janusz; Cybula, Magdalena; Pietruszewska, Wioletta; Zielińska-Kaźmierska, Bogna; Józefowicz-Korczyńska, Magdalena

doi:10.5114/aoms.2017.72405

Cited by 9 publications

(13 citation statements)

References 29 publications

(42 reference statements)

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“…Riedel et al discovered the elevation of serum MMP-9 levels in patients with head and neck SCC [ 43 ], which is also observed by Stanciu et al [ 44 ]. Lotfi et al reported that both serum MMP-2 and MMP-9 levels were significantly increased in laryngeal SCC cases compared with healthy controls [ 45 ], and similar results were depicted by Matulka et al and Grzelczyk et al [ 46 , 47 ]. Choudhry et al revealed that serum levels of MMP-1, − 8, − 10, − 12 and − 13 in oral SCC patients were substantially elevated as compared with healthy controls [ 48 ].…”

Section: Discussionsupporting

confidence: 66%

“…Measurement of serum MMP levels in patients with SCC of different anatomic sites, and comparison of the results with those of healthy controls have been documented [42][43][44][45][46][47][48][49][50]. Jiao et al showed that patients with esophageal SCC had significantly higher serum MMP-13 levels than healthy controls; furthermore, serum MMP-13 levels were found to be associated with tumor progression and survival [42].…”

Section: Discussionmentioning

confidence: 99%

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Serum matrix metalloproteinase-13 as a diagnostic biomarker for cutaneous squamous cell carcinoma

Wang

Yan

et al. 2021

BMC Cancer

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Background A significant proportion of newly diagnosed patients with cutaneous squamous cell carcinoma (cSCC) have metastasis and eventually die of the disease, necessitating the exploration of novel biomarkers for early detection of cSCC aggressiveness, risk assessment and monitoring. Matrix metalloproteinase-13 (MMP-13) has been implicated in cSCC pathogenesis. Serum MMP-13 levels have been shown to predict survival in patients with esophageal SCC, but their diagnostic value for cSCC has not been explored. Methods We conducted a case-control study to examine serum MMP-13 as a biomarker for cSCC. Patients with cSCC undergoing surgical resection and health controls undergoing plastic surgery were recruited. ELISA for measurement of serum MMP-13 and immunohistochemistry for detection of tissue MMP-13 were performed, and the results were compared between the case and the control group, and among different patient groups. ROC curve analysis was performed to determine the diagnostic value of serum MMP-13 levels. Results The ratio of male to female, and the age between the case (n = 77) and the control group (n = 50) were not significantly different. Patients had significantly higher serum MMP-13 levels than healthy controls. Subjects with stage 3 cSCC had markedly higher serum MMP-13 levels than those with stage 1 and stage 2 cSCC. Patients with invasive cSCC had remarkably higher serum MMP-13 than those with cSCC in situ. Post-surgery serum MMP-13 measurement was done in 12 patients, and a significant MMP-13 decrease was observed after removal of cSCC. Tumor tissues had a remarkably higher level of MMP-13 than control tissues. Serum MMP-13 predicted the presence of invasive cSCC with an AUC of 0.87 (95% CI [0.78 to 0.95]) for sensitivity and specificity of 81.7 and 82.4%, respectively for a cut-off value of 290 pg/mL. Serum MMP-13 predicted lymph node involvement with an AUC of 0.94 (95% CI [0.88 to 0.99]) for sensitivity and specificity of 93.8 and 88.5%, respectively for a cut-off value of 430 pg/mL. Conclusion Serum MMP-13 might serve as a valuable biomarker for early detection of cSCC invasiveness and monitoring of cSCC progression.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Serum matrix metalloproteinase-13 as a diagnostic biomarker for cutaneous squamous cell carcinoma

Wang

Yan

et al. 2021

BMC Cancer

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“…MMP‐9 mediates pepsin‐induced mucin 5AC expression in airway epithelial cells contributing to hypersecretion and inflammation, 73 is induced by TGF‐β signaling in tracheal cells, a key pathway in laryngotracheal stenosis, 74 is elevated in mild and severe GERD, 75 and plays a role in the early inflammatory response in a model of Barrett's esophagus (BE) 76 . MMP‐2, 7 and 9 have been implicated in laryngeal cancer 77 . MMP‐1 is a pre‐invasive factor for BE associated with GERD severity and esophageal adenocarcinoma (EAC) 78,79 .…”

Section: Discussionmentioning

confidence: 99%

Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

Samuels

Blaine-Sauer

Yan

et al. 2023

Laryngoscope Investig Oto

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BackgroundLaryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and can promote laryngeal carcinogenesis. More than 20% of the US population suffers from LPR and there is no effective medical therapy. Pepsin is a predominant source of damage during LPR which disrupts laryngeal barrier function potentially via E‐cadherin cleavage proteolysis and downstream matrix metalloproteinase (MMP) dysregulation. Fosamprenavir (FDA‐approved HIV therapeutic and prodrug of amprenavir) is a pepsin‐inhibiting LPR therapeutic candidate shown to rescue damage in an LPR mouse model. This study aimed to examine amprenavir protection against laryngeal monolayer disruption and related E‐cadherin proteolysis and MMP dysregulation in vitro.MethodsLaryngeal (TVC HPV) cells were exposed to buffered saline, pH 7.4 or pH 4 ± 1 mg/mL pepsin ± amprenavir (10–60 min). Analysis was performed by microscopy, Western blot, and real time polymerase chain reaction (qPCR).ResultsAmprenavir (1 μM) rescued pepsin acid‐mediated cell dissociation (p < .05). Pepsin acid caused E‐cadherin cleavage indicative of regulated intramembrane proteolysis (RIP) and increased MMP‐1,3,7,9,14 24‐h postexposure (p < .05). Acid alone did not cause cell dissociation or E‐cadherin cleavage. Amprenavir (10 μM) protected against E‐cadherin cleavage and MMP‐1,9,14 induction (p < .05).ConclusionsAmprenavir, at serum concentrations achievable provided the manufacturer's recommended dose of fosamprenavir for HIV, protects against pepsin‐mediated cell dissociation, E‐cadherin cleavage, and MMP dysregulation thought to contribute to barrier dysfunction and related symptoms during LPR. Fosamprenavir to amprenavir conversion by laryngeal epithelia, serum and saliva, and relative drug efficacies in an LPR mouse model are under investigation to inform development of inhaled formulations for LPR.

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“…Laryngeal squamous cell carcinoma (LSCC) is a multifactorial disease characterized by frequent metastasis in lymph nodes early during disease onset, and represents the most common form of head and neck malignancies 1 . Recent evidence indicates a clear association between altered growth factor receptors-mediated intracellular pathways and biological processes underlying LSCC that induce changes in the extracellular matrix (ECM) 2,3 . Lumican is an important ECM protein that belongs to a class II small leucine rich proteoglycans and has four potential N-glycosylation sites 4 .…”

Section: Introductionmentioning

confidence: 99%

Different expression of lumican glycoforms in non-metastatic and metastatic laryngeal squamous cell carcinoma

Car

Visentin

Đanić

et al. 2021

Med. Flum. (Online)

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Objective: Association of altered growth factor receptors-mediated intracellular pathways and biological processes associated with extracellular matrix composition and structure in laryngeal squamous cell carcinoma (LSCC) were described previously. In particular, the expression and glycosylation of important extracellular matrix molecules (ECM) such as small leucine rich proteoglycan lumican, may be generally associated with disrupted extracellular matrix integrity and inflammation processes which have a role in tumour invasiveness. In this study, the relative expression of different lumican glycoforms were evaluated in primary tumour and tumour-unaffected tissue samples of ten patients with metastatic and ten non-metastatic LSCC by Western blot and 2D immunoblot analysis. Materials and methods: Tissue samples from the primary tumours and paired adjacent non-tumour tissues were surgically resected from ten untreated LSCC patients with non-metastatic disease and ten LSCC patients with lymph nodes metastases. The relative expression of different lumican glycoforms in primary tumours and paired adjacent non-tumour tissues were evaluated by Western blot and 2D immunoblot analysis. Results: Results of Western blot analysis have revealed elevated expression of the moderately glycosylated lumican form in metastatic (p<0,05) and non-metastatic primary tumour tissues in comparison with tumour unaffected tissues. In addition, moderately glycosylated form of lumican with negatively charged oligosaccharide residues in the N-glycan molecule part was exclusively determined in metastatic primary tumour tissues by 2D immunoblot analysis. Conclusion: We demonstrated elevated expression of the moderately glycosylated lumican form with negatively charged oligosaccharide residues in the N-glycan portion exclusively in primary laryngeal squamous cell carcinoma from patients with metastatic disease.

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Matrix metalloproteinases, inhibitor of metalloproteinases mRNA and protein expression in laryngeal squamous cell carcinoma

Cited by 9 publications

References 29 publications

Serum matrix metalloproteinase-13 as a diagnostic biomarker for cutaneous squamous cell carcinoma

Serum matrix metalloproteinase-13 as a diagnostic biomarker for cutaneous squamous cell carcinoma

Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

Different expression of lumican glycoforms in non-metastatic and metastatic laryngeal squamous cell carcinoma

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