Non-invasive profiling of protease-specific elastin turnover in lung cancer: biomarker potential.
PURPOSE:
Elastin is a signature protein of lungs. Increased elastin turnover driven by altered proteolytic activity is an important part of lung tumorigenesis. Elastin-derived fragments have been shown to be pro-tumorigenic, however, little is known regarding the biomarker potential of such elastin…
Authors:
- Thoracius-Ussing J,
- Kehlet SN,
- Rønnow S,
- Karsdal MA,
- Willumsen N,
A fragment of SPARC reflecting increased collagen affinity shows pathological relevance in lung cancer - implications of a new collagen chaperone function of SPARC
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…
Journal:
Authors:
- Kehlet SN,
- Manon-Jensen T,
- Sun S,
- Brix S,
- Karsdal MA,
- Leeming DJ,
- Willumsen N,
Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix
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 c…
Journal:
Authors:
- Kehlet SN,
- Willumsen N,
- Armbrecht G,
- Dietzel R,
- Brix S,
- Henriksen K,
- Karsdal MA,
Cathepsin-S degraded decorin are elevated in fibrotic lung disorders - development and biological validation of a new serum biomarker
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 h…
Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Brix S,
- Curran M,
- Brodmerkel C,
- Dasgupta B,
- Willumsen N,
- Bager CL,
- Kehlet SN,
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
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 …
Journal:
Authors:
- Willumsen N,
- Bager CL,
- Bay-Jensen AC,
- Kehlet SN,
- Harling H,
- Leeming DJ,
- Karsdal MA,
- Jorgensen LN,
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
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 predict…
Journal:
Authors:
- Willumsen N,
- Bager CL,
- Kehlet SN,
- Dragsbaek K,
- Neergaard JS,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Lipton A,
- Christiansen C,
- Karsdal MA,
Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study
The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…
Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Kehlet SN,
- Hansen HB,
- Hansen G,
- Byrjalsen I,
- Alexandersen P,
- Lindgren LM,
- Bihlet AR,
- Riis BJ,
- Andersen JR,
- Qvist P,
- Karsdal MA,
- Christiansen C,
Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote…
Journal:
Authors:
- Kehlet SN,
- Sanz-Pamplona R,
- Brix S,
- Leeming DJ,
- Karsdal MA,
- Moreno V,
Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study
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 t…
Journal:
Authors:
- Bager CL,
- Willumsen N,
- Kehlet SN,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Høgdall E,
- Karsdal MA,
Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Hansen HB,
- Byrjalsen I,
- Alexandersen P,
- Kehlet SN,
- Bay-Jensen AC,
- Christiansen C,
- Karsdal MA,