MMP Mediated Degradation of Type IV Collagen Alpha 1 and Alpha 3 Chains Reflects Basement Membrane Remodeling in Experimental and Clinical Fibrosis – Validation of Two Novel Biomarker Assays

Sand, J.M.B.; Larsen, Lise; Hogaboam, Cory M.; Martínez, Fernando J.; Han, MeiLan K.; Larsen, Martin R.; Nawrocki, Arkadiusz; Zheng, Qinlong; Karsdal, Morten A.; Leeming, Diana Julie

doi:10.1371/journal.pone.0084934

Cited by 156 publications

(151 citation statements)

References 59 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…Tumor cells overproduce MMP-9, leading to the degradation of type IV collagen and the basement membrane, which disrupts tissue architecture and function (55). The present findings are consistent with previous studies, which suggested that MMP-9 plays a role in bladder cancer (56,57).…”

Section: A B Csupporting

confidence: 92%

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Zeng

Cen²,

Kang³

2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. The present study investigated the potential association between matrix metalloproteinase-9 (MMP-9) expression and the pathogenesis of bladder cancer. The present study reviewed previous studies published in Chinese and English using predefined selection criteria, which identified high-quality studies concerning MMP-9 and bladder cancer. Statistical analyses of the data were conducted using Comprehensive Meta-Analysis software version 2.0. In total, 23 case-control studies were selected, which consisted of 1,040 bladder cancer patients and 244 healthy controls. The expression rates and protein levels of MMP-9 were significantly increased in bladder cancer patients compared with the healthy controls, which was demonstrated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay-based methods. Furthermore, the expression rate of MMP-9 in histological G1/G2 grade bladder cancer tumors was significantly decreased compared with G3 tumors. Subgroup analysis based on ethnicity demonstrated that the rate of MMP-9 protein expression between bladder cancer patients and healthy controls was significantly different in African, Asian and Caucasian patients, which was identified using IHC. The MMP-9 protein levels in bladder cancer patients and healthy controls were significantly different between Asian and Caucasian patients, but not African patients. The differences between MMP-9 expression in ethnic groups were also evident in the expression rate of MMP-9 identified in histological G1/G2 grade tumors in Asian and Caucasian patients compared with G3 grade tumors, which was not evident in African patients. In conclusion, the present meta-analysis results markedly indicate that MMP-9 expression is associated with clinicopathological features of bladder cancer, suggesting that MMP-9 may be a useful biomarker in the diagnosis and clinical management of bladder cancer, and may be a valuable therapeutic target. IntroductionWorldwide, bladder cancer is the 7th most common cancer in men and the 17th most common cancer in women (1). Notably, in the developed world, bladder cancer ranks as the 4th and 9th most common cancer in men and women, respectively (2). An estimated 375,000 bladder cancer cases are reported each year around the world, with 68,810 novel cases and ~14,100 mortalities reported in the United States in 2013 (3). Transitional cell carcinoma is the most frequently occurring type of bladder cancer. Other bladder cancer types consist of adenocarcinoma, squamous cell carcinoma and small cell bladder cancer (4,5). Notably, the incidence of bladder cancer increases with age, particularly in men (6). Bladder cancer arises as a result of multistep alterations, among which metastasis is crucial (7). Epidemiological studies have demonstrated that several environmental factors may contribute to bladder cancer risk, including smoking, chronic inflammation, radiation exposure, anticancer drugs and aromatic amines, which are contained in dyes (6,8). The treatment of bladder cancer is based on multiple para...

show abstract

Section: A B Csupporting

confidence: 92%

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Zeng

Cen²,

Kang³

2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…C4M reflects basement membrane (BM) remodeling and invasion, and measures a type IV collagen a1-chain fragment generated by cleavage with MMP-12 (7). A hallmark of the malignant process is the acquisition of an invasive phenotype that enables malignant cells to invade the BM (13).…”

Section: Introductionmentioning

confidence: 99%

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

Bager

Willumsen

Kehlet

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study.Methods: Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and

show abstract

“…Using well-characterized and validated competitive ELISAs, levels of MMP 2, 9 and 13-degraded collagen type I (C1M) [10], MMP-9 degraded collagen type III (C3M) [11], and MMP-9 and 12 degraded collagen type IV (C4M, C4M12) [12,13] were assessed in the serum samples.…”

Section: Elisa Measurements and Proceduresmentioning

confidence: 99%

Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study

Bager

Willumsen

Leeming

et al. 2015

CBM

View full text Add to dashboard Cite

Abstract. BACKGROUND: During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments (e.g. collagens) to the circulation, which when measured may reflect disease pathogenesis. OBJECTIVE: To investigate if biomarkers of protease-degraded collagen could differentiate ovarian and breast cancer patients from healthy controls when measured in serum. METHODS: The levels of markers reflecting MMP-degradation of type I (C1M), type III (C3M) and type IV (C4M, C4M12) collagen were assessed in serum from ovarian cancer patients (n = 10), breast cancer patients (n = 14) and healthy controls (n = 49) using validated ELISAs. The markers were compared using one way ANOVA and AUC was calculated. RESULTS: All markers were significantly elevated in serum from ovarian cancer patients (p < 0.0001) and breast cancer patients (p < 0.04-0.0001) compared to healthy controls. Furthermore, diagnostically the markers were able to differentiate ovarian (AUROC 90%-93%) and breast cancer patients (AUROC 76%-93%) from healthy controls, with C1M being the strongest differentiator of disease vs. controls. CONCLUSION: Four serum biomarkers reflecting altered MMP-mediated collagen turnover were able to differentiate ovarian and breast cancer patients from healthy controls.Keywords: Cancer, extracellular matrix, collagen, biomarkers, breast cancer, ovarian cancer, matrix metalloproteinase, degradation, remodeling, tumor microenvironment BackgroundWomen's health is significantly influenced by the occurrence of cancers, such as breast and ovarian can- cers. Breast cancer is the leading cause of cancer death among women in the US and EU [1,2], and ovarian cancer, although less frequent, is often discovered in the late clinical stages where the cancer has already spread and no curative interventions are possible [3]. Taken together, the medical needs for breast and ovarian cancer are early diagnosis, prognosis and prediction of a therapeutic response. One of the best ways to achieve this is to use serum biomarkers [4].

show abstract

MMP Mediated Degradation of Type IV Collagen Alpha 1 and Alpha 3 Chains Reflects Basement Membrane Remodeling in Experimental and Clinical Fibrosis – Validation of Two Novel Biomarker Assays

Cited by 156 publications

References 59 publications

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

Collagen degradation products measured in serum can separate ovarian and breast cancer patients from healthy controls: A preliminary study

Contact Info

Product

Resources

About