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A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer – implications of a new collagen chaperone function of SPARC.

January 1, 2018

Cancer Biol Ther

Abstract The matricellular protein SPARC (secreted proteome acidic and rich in cysteine) is known to bind collagens and regulate fibrillogenesis. Cleavage of SPARC at a single peptide bond, increases the affinity for collagens up to 20-fold. To investigate if this specific cleavage has pathological relevance in fibrotic disorders, we developed a competitive ELISA targeting the […]

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Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix.

January 1, 2018

PLoS One

Abstract The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small collagen fragments are released into the circulation, which act […]

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Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities.

January 1, 2018

Cancer Immunol Immunother

Abstract Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Tumor […]

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Cathepsin-S degraded decorin are elevated in fibrotic lung disorders – development and biological validation of a new serum biomarker.

August 9, 2017

BMC Pulm Med

Abstract BACKGROUND Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue homeostasis contributing to extracellular matrix remodeling diseases. Here, we present […]

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Excessive matrix metalloprotease-mediated degradation of interstitial tissue (type I collagen) independently predicts short-term survival in an observational study of postmenopausal women diagnosed with cancer.

August 8, 2017

Oncotarget

Abstract Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predictive of cancer-specific mortality. Between 1999 and 2001, 5855 Danish postmenopausal women […]

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Unique insight into microenvironmental changes in colorectal cancer: Ex vivo assessment of matrix metalloprotease-mediated molecular changes in human colorectal tumor tissue and corresponding non-neoplastic adjacent tissue.

May 1, 2017

Oncol Lett

Abstract Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the dynamic processes of the MMP-mediated degradation of signature proteins from colorectal tissue. The aim of the […]

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Nidogen-1 Degraded by Cathepsin S can be Quantified in Serum and is Associated with Non-Small Cell Lung Cancer.

April 1, 2017

Neoplasia

Abstract Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential in cancer. The aim of this study was to investigate if […]

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Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling.

September 16, 2016

Biochem Biophys Res Commun

Abstract Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the ECM is fibronectin. Fibronectin serves as an adhesion molecule anchoring cells to the underlying basement membrane […]

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

September 1, 2016

Cancer Epidemiol Biomarkers Prev

Abstract 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 […]

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Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling.

August 1, 2016

Clin Biochem

Abstract OBJECTIVES Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive enzyme-linked immunosorbent assay (ELISA) targeting type VIII collagen in serum and […]

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