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)

Diana Julie Leeming; Y. He; S. S. Veidal; Q. H. T. Nguyen; D. V. Larsen; M. Koizumi; T. Segovia-Silvestre; C. Zhang; Q. Zheng; S. Sun; Y. Cao; Vibeke Barkholt; Per Hägglund; A. C. Bay-Jensen; P. Qvist; M. A. Karsdal

doi:10.3109/1354750x.2011.620628

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)

Diana Julie Leeming, Y. He, S. S. Veidal, Q. H. T. Nguyen, D. V. Larsen, M. Koizumi, T. Segovia-Silvestre, C. Zhang, Q. Zheng, S. Sun, Y. Cao, Vibeke Barkholt, Per Hägglund, A. C. Bay-Jensen, P. Qvist, M. A. Karsdal

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

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.

Original language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	16
Issue number	7
Pages (from-to)	616-628
Number of pages	13
ISSN	1055-9965
DOIs	https://doi.org/10.3109/1354750x.2011.620628
Publication status	Published - 2011

Keywords

Biochemical markers
Type I collagen
Liver fibrosis
Protease-cleaved neo-epitope
MMP-2,-9,-13
Translational science
Bile duct ligation
CCL4
Rat model
Breast cancer
Prostate cancer
Bone metastases

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10.3109/1354750x.2011.620628

Cite this

Leeming, D. J., He, Y., Veidal, S. S., Nguyen, Q. H. T., 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. (2011). 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). Cancer Epidemiology, Biomarkers & Prevention, 16(7), 616-628. https://doi.org/10.3109/1354750x.2011.620628

Leeming, Diana Julie ; He, Y. ; Veidal, S. S. ; Nguyen, Q. H. T. ; Larsen, D. V. ; Koizumi, M. ; Segovia-Silvestre, T. ; Zhang, C. ; Zheng, Q. ; Sun, S. ; Cao, Y. ; Barkholt, Vibeke ; Hägglund, Per ; Bay-Jensen, A. C. ; Qvist, P. ; Karsdal, M. A. / 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). In: Cancer Epidemiology, Biomarkers & Prevention. 2011 ; Vol. 16, No. 7. pp. 616-628.

@article{76453063ff614473b43517215d2b702a,

title = "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)",

abstract = "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.",

keywords = "Biochemical markers, Type I collagen, Liver fibrosis, Protease-cleaved neo-epitope, MMP-2,-9,-13, Translational science, Bile duct ligation, CCL4, Rat model, Breast cancer, Prostate cancer, Bone metastases",

author = "Leeming, {Diana Julie} and Y. He and Veidal, {S. S.} and Nguyen, {Q. H. T.} and Larsen, {D. V.} and M. Koizumi and T. Segovia-Silvestre and C. Zhang and Q. Zheng and S. Sun and Y. Cao and Vibeke Barkholt and Per H{\"a}gglund and Bay-Jensen, {A. C.} and P. Qvist and Karsdal, {M. A.}",

year = "2011",

doi = "10.3109/1354750x.2011.620628",

language = "English",

volume = "16",

pages = "616--628",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "7",

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Leeming, DJ, He, Y, Veidal, SS, Nguyen, QHT, Larsen, DV, Koizumi, M, Segovia-Silvestre, T, Zhang, C, Zheng, Q, Sun, S, Cao, Y, Barkholt, V, Hägglund, P, Bay-Jensen, AC, Qvist, P & Karsdal, MA 2011, '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)', Cancer Epidemiology, Biomarkers & Prevention, vol. 16, no. 7, pp. 616-628. https://doi.org/10.3109/1354750x.2011.620628

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, Diana Julie; He, Y.; Veidal, S. S.; Nguyen, Q. H. T.; Larsen, D. V.; Koizumi, M.; Segovia-Silvestre, T.; Zhang, C.; Zheng, Q.; Sun, S.; Cao, Y.; Barkholt, Vibeke; Hägglund, Per; Bay-Jensen, A. C.; Qvist, P.; Karsdal, M. A.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 16, No. 7, 2011, p. 616-628.

Research output: Contribution to journal › Journal article › Research › peer-review

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T1 - 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)

AU - Leeming, Diana Julie

AU - He, Y.

AU - Veidal, S. S.

AU - Nguyen, Q. H. T.

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, Vibeke

AU - Hägglund, Per

AU - Bay-Jensen, A. C.

AU - Qvist, P.

AU - Karsdal, M. A.

PY - 2011

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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 - Biochemical markers

KW - Type I collagen

KW - Liver fibrosis

KW - Protease-cleaved neo-epitope

KW - MMP-2,-9,-13

KW - Translational science

KW - Bile duct ligation

KW - CCL4

KW - Rat model

KW - Breast cancer

KW - Prostate cancer

KW - Bone metastases

U2 - 10.3109/1354750x.2011.620628

DO - 10.3109/1354750x.2011.620628

M3 - Journal article

VL - 16

SP - 616

EP - 628

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 7

ER -