A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)
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A novel marker for assessment of liver matrix remodeling : An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M). / Leeming, D. J.; He, Y.; Veidal, S. S.; Nguyen, QHT; Larsen, D. V.; Koizumi, M.; Segovia-Silvestre, T.; Zhang, C.; Zheng, Q.; Sun, S.; Cao, Y.; Barkholt, V.; Hägglund, P.; Bay-Jensen, A. C.; Qvist, P.; Karsdal, M. A.
In: Biomarkers, Vol. 16, No. 7, 01.11.2011, p. 616-628.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A novel marker for assessment of liver matrix remodeling
T2 - An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)
AU - Leeming, D. J.
AU - He, Y.
AU - Veidal, S. S.
AU - Nguyen, QHT
AU - Larsen, D. V.
AU - Koizumi, M.
AU - Segovia-Silvestre, T.
AU - Zhang, C.
AU - Zheng, Q.
AU - Sun, S.
AU - Cao, Y.
AU - Barkholt, V.
AU - Hägglund, P.
AU - Bay-Jensen, A. C.
AU - Qvist, P.
AU - Karsdal, M. A.
PY - 2011/11/1
Y1 - 2011/11/1
N2 - A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further evaluated in a clinical study of prostate-, lung- and breast-cancer patients stratified according to skeletal metastases. A technically robust ELISA assay specific for a MMP-2, -9 and -13 neo-epitope was produced and seen to be statistically elevated in BDL rats compared to baseline levels as well as significantly elevated in CCL4 rats stratified according to the amount of total collagen in the livers. CO1-764 levels also correlated significantly with total liver collagen and type I collagen mRNA expression in the livers. Finally, the CO1-764 marker was not correlated with skeletal involvement or number of bone metastases. This ELISA has the potential to assess the degree of liver fibrosis in a non-invasive manner.
AB - A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further evaluated in a clinical study of prostate-, lung- and breast-cancer patients stratified according to skeletal metastases. A technically robust ELISA assay specific for a MMP-2, -9 and -13 neo-epitope was produced and seen to be statistically elevated in BDL rats compared to baseline levels as well as significantly elevated in CCL4 rats stratified according to the amount of total collagen in the livers. CO1-764 levels also correlated significantly with total liver collagen and type I collagen mRNA expression in the livers. Finally, the CO1-764 marker was not correlated with skeletal involvement or number of bone metastases. This ELISA has the potential to assess the degree of liver fibrosis in a non-invasive manner.
KW - bile duct ligation
KW - Biochemical markers
KW - bone metastases
KW - breast cancer
KW - CCL4
KW - liver fibrosis
KW - MMP-2,-9,-13
KW - prostate cancer
KW - protease-cleaved neo-epitope
KW - rat model
KW - translational science
KW - type I collagen
U2 - 10.3109/1354750X.2011.620628
DO - 10.3109/1354750X.2011.620628
M3 - Journal article
C2 - 21988680
AN - SCOPUS:80054906939
VL - 16
SP - 616
EP - 628
JO - Biomarkers
JF - Biomarkers
SN - 1354-750X
IS - 7
ER -
ID: 240160089