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 journalJournal articleResearchpeer-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 languageEnglish
    JournalCancer Epidemiology, Biomarkers & Prevention
    Volume16
    Issue number7
    Pages (from-to)616-628
    Number of pages13
    ISSN1055-9965
    DOIs
    Publication statusPublished - 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

    Cite this

    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",

    }

    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 journalJournal articleResearchpeer-review

    TY - JOUR

    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

    Y1 - 2011

    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 -