A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall sur...
January 19, 2021
Journal:
Sci Rep
Author:
Nissen NI, Kehlet S, Boisen MK, Liljefors M, Jensen C, Johansen AZ, Johansen JS, Erler JT, Karsdal M, Mortensen JH, Høye A, Willumsen N
Background: Immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) receptor induce a response in only a subgroup of patients with metastatic melanoma. Previous research suggests that transforming growth factor beta signaling and a collagen-rich peritumoral stroma (tumor ...
October 8, 2020
Journal:
J Immunother Cancer
Author:
Hurkmans DP, Jensen C, Koolen SLW, Aerts J, Karsdal MA, Mathijssen RHJ, Willumsen N
A T-cell permissive tumor microenvironment, characterized by the presence of activated T cells and low fibrotic activity is crucial for response to immune checkpoint inhibitors (ICIs). Granzyme B has been shown to promote T-cell migration through the basement membrane by the degradation of type IV c...
September 20, 2020
Journal:
Cancers (Basel)
Author:
Jensen C, Sinkeviciute D, Madsen DH, Önnerfjord P, Hansen M, Schmidt H, Karsdal MA, Svane IM, Willumsen N
Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring...
April 3, 2020
Journal:
Sci Rep
Author:
Nielsen SH, Mortensen JH, Willumsen N, guldager Kring Rasmussen D, Mogensen DJ, Di Sabatino A, Mazza G, Jørgensen LN, giuffrida P, Pinzani M, Klinge LG, Kjeldsen J, Leeming DJ, Karsdal MA, Genovese F
Background: Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis. Objective: We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in ingui...
January 3, 2020
Journal:
J Nutr
Author:
Kjaer M, Frederiksen AKS, Nissen NI, Willumsen N, Van Hall G, Jorgensen LN, Andersen JR, Årgen MS
Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular ...
December 24, 2019
Journal:
Sci Rep
Author:
Willumsen N, Ali SM, Leitzel K, Drabick JJ, Yee N, Polimera HV, Nagabhairu V, Krecko L, Ali A, Maddukuri A, Moku P, Poullose J, Menon H, Pancholy N, Costa L, Karsdal MA, Lipton A
Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular ...
December 24, 2019
Journal:
Sci Rep
Author:
Willumsen N, Ali SM, Leitzel K, Drabick JJ, Yee N, Polimera HV, Nagabhairu V, Krecko L, Ali A, Maddukuri A, Moku P, Poullose J, Menon H, Pancholy N, Costa L, Karsdal MA, Lipton A
Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular ...
December 24, 2019
Journal:
Sci Rep
Author:
Willumsen N, Ali SM, Leitzel K, Drabick JJ, Yee N, Polimera HV, Nagabhairu V, Krecko L, Ali A, Maddukuri A, Moku P, Poullose J, Menon H, Pancholy N, Costa L, Karsdal MA, Lipton A
Introduction: Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out...
Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. The aim of this biomarker study was to determine the clinical utility of serum HA and the propept...
October 23, 2019
Journal:
Int J Cancer
Author:
Chem IM, Willumsen N, Dehlendorff C, Johansen AZ, Jensen BV, Hansen CP, Hasselby JP, Bojesen SE, Pfeiffer P, Nielsen Se, Holländer NH, Yilmaz Mk, Karsdal MA, Johansen JS
Background: Remodeling of extracellular matrix through collagen degradation is a crucial step in the metastatic cascade. The aim of this study was to evaluate the potential clinical relevance of the serum collagen degradation markers (CDM) C3M and C4M during neoadjuvant chemotherapy for breast cance...
August 15, 2019
Journal:
Cancers (Basel)
Author:
Banys-Paluchowski M, Loibl S, Witzel I, Mundhenke C, Lederer B, Solbach C, Karn T, Marmé F, Nekljudova V, Schem C, Stickeler E, Willumsen N, Karsdal MA, Untch M, Müller V
BACKGROUND: Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activa...
The extracellular matrix (ECM) plays an important role in cancer progression. It can be divided into the basement membrane (BM) that supports epithelial/endothelial cell behavior and the interstitial matrix (IM) that supports the underlying stromal compartment. The major components of the ECM are th...
March 6, 2019
Journal:
Journal of Experimental Clinical Cancer Research
Author:
Nissen N, Karsdal MA, Willumsen N
OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which h...
February 12, 2019
Journal:
Transl Oncol
Author:
Holm Nielsen S, Willumsen N, Leeming DJ, Daniels SJ, brix s, Karsdal MA, Genovese F, Nielsen MJ
BACKGROUND: Excessive extracellular matrix (ECM) remodeling and a reactive stroma can affect T-cell infiltration and T-cell activity in the tumor and hereby influence response to immune checkpoint inhibitors (ICI). In the pursuit of finding biomarkers that predict treatment response, we evaluated th...
December 19, 2018
Journal:
Br J Clin Pharmacol
Author:
Jensen C, Madsen DH, Hansen M, Schmidt H, Svane IM, Karsdal MA, Willumsen N
December 19, 2018
Journal:
J Inmunother Cancer
Author:
jensen C, Madsen DH, hansen M, Schmidt H, Svane IM, Karsdal MA, Willumsen N
OBJECTIVES: Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation. DESIGN ...
November 30, 2018
Journal:
Biochem Biophys Rep
Author:
Leeming DJ, Willumsen N, Sand JM, Holm Nielsen S, Dasgupta B, Brodmerkel C, Bager CL, Karsdal MA
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 ...
November 22, 2018
Journal:
Journal Of Cancer Research And Clinical Oncology
Author:
Thoracius-Ussing J, Kehlet SN, Rønnow S, Karsdal MA, Willumsen N
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...
August 1, 2018
Journal:
Cancer biology therapy
Author:
Kehlet SN, Manon-Jensen T, Sun S, Brix S, Karsdal MA, Leeming DJ, Willumsen N
Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have bioma...
July 20, 2018
Journal:
Cancer Med
Author:
Jensen C, Nielsen SH, Mortensen JH, Kjeldsen J, Klinge LG, Harling H, Jørgensen LN, Karsdal MA, Willumsen N, Leeming DJ
BACKGROUND: The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of post-menopausal women. METHODS: 5,855 postmenopausal Danish women ...
July 14, 2018
Journal:
J Gerontol A Biol Sci Med Sci
Author:
Bager CL, Willumsen N, Bay-Jensen AC, Nielsen HB, Karsdal MA
Increased extracellular matrix (ECM) formation and matrix metalloprotease (MMP)-mediated ECM degradation are parts of tumorgenesis and generates collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in serum with outcomes in two i...
June 20, 2018
Journal:
Int j.cancer, International journal of cancer
Author:
Lipton A, Leitzel K, Polimera HV, Ali SM, Naggabhairu V, Marks E, Richardson AE, Krecko L, Ali A, Koestler W, Esteva FJ, Leeming DJ, Karsdal MA, Willumsen N
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...
March 29, 2018
Journal:
PLoS One
Author:
Kehlet SN, Willumsen N, Armbrecht G, Dietzel R, Brix S, Henriksen K, Karsdal MA
OBJECTIVES: Fibrosis and cancer are characterized by extracellular matrix (ECM) remodeling. The basement membrane is mainly composed by collagen type IV and laminin. Tumstatin is a matrix metalloproteinase-9 (MMP-9) generated matrikine of collagen type IV α3 chain. We evaluated the potential of tums...
March 7, 2018
Journal:
Transl Oncol
Author:
Nielsen SH, Willumsen N, Brix S, Sun S, Manon-Jensen T, Karsdal MA, Genovese F
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 n...
November 8, 2017
Journal:
Cancer Immunol Immunother
Author:
Willumsen N, Thomsen LB, Bager CL, Jensen C, Karsdal MA
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 ho...
August 9, 2017
Journal:
BMC Pulm Med.
Author:
Karsdal MA, Leeming DJ, Brix S, Curran M, Brodmerkel C, Dasgupta B, Willumsen N, Bager CL, Kehlet SN
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 ...
May 13, 2017
Journal:
Oncol Lett
Author:
Willumsen N, Bager CL, Bay-Jensen AC, Kehlet SN, Harling H, Leeming DJ, Karsdal MA, Jorgensen LN
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 ...
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...
February 11, 2017
Journal:
Oncotarget
Author:
Willumsen N, Bager CL, Kehlet SN, Dragsbaek K, Neergaard JS, Hansen HB, Bay-Jensen AC, Leeming DJ, Lipton A, Christiansen C, Karsdal MA
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...
August 1, 2016
Journal:
Clin Biochem
Author:
Hansen NU, Willumsen N, Sand JM, Larsen L, Karsdal MA, Leeming DJ
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