Author: Claire Hornung

Evaluating CAFs Activity and Collagen Expression Profiles Using Clinically Validated Biomarkers

Posted on by Claire Hornung

Evaluating cancer-associated fibroblasts activity and collagen expression profiles using clinically validated biomarkers

Introduction

Cancer-associated fibroblasts (CAFs) are pivotal orchestrators of tumor progression through their modulation of the extracellular matrix (ECM), particularly via the deposition of collagen. Different stimuli (e.g. TGF-β, PDGF-AB, IL-1α) can activate fibroblasts and induce phenotypic alterations in CAFs, promoting a pro-tumorigenic microenvironment characterized by enhanced ECM synthesis and remodeling. Known for their heterogeneity across tumors, their collagen expression and fibrotic activity patterns remain unclear.

In this study we aimed to elucidate differences in collagen production among various CAF subtypes from different cancer tissues, using non-invasive biomarkers to identify distinct expression profiles and fibrotic activity levels.

Poster

MBE2024 CAFs activity_Nordic BioscienceDownload

Conclusion

These findings underscore the heterogeneity in collagen production and fibrotic activity among CAFs from different indications, providing valuable insights into the ECM dynamics within distinct TMEs. Collagen-based non-invasive biomarkers demonstrate the capability to differentiate between the fibrotic activity of CAFs isolated from different tissues.

Get in touch

Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
+45 4452 5252 Contact us via email!

    Metabolic Activation of Fibroblasts in Obesity and Related Disorders

    Posted on by Claire Hornung

    In this webinar leading experts will discuss the critical role fibroblasts play in metabolic disorders. The presentations will highlight recent research findings and explore the therapeutic potential of modulating fibroblast activity to improve patient outcomes.

    Agenda

    Opening of the session

    Metabolic activation of ECM production of fibroblast and the relation to outcomes in heart, liver and kidney diseases – Dr. Morten Karsdal

    Metabolic activation and de-activation of fibroblasts in MAFLD by weight loss. The weight-dependent angle – Dr. Jörn M. Schattenberg

    Pharmacological modulation of fibroblast activation and the benefit for patients –Dr. Diana J. Leeming

    General discussion and questions

    Scientific topics

    We will explore key aspects of fibroblast activity in metabolic health, starting with the metabolic activation and deactivation of fibroblasts in MAFLD (Metabolic Associated Fatty Liver Disease). It highlights the weight-dependent factors influencing these processes and the impact of weight loss on fibroblast behavior in MAFLD.

    The discussion then moves to the metabolic activation of extracellular matrix (ECM) production by fibroblasts and its effects on heart, liver, and kidney diseases. Finally, it addresses the potential benefits of pharmacological interventions in modulating fibroblast activation, offering therapeutic possibilities for patients with these conditions.

    Watch the replay here

    Prof. Dr. Jörn M. Schattenberg

    • Dr. Jörn M. Schattenberg is a Professor of Medicine and Director of the Department of Medicine II at Saarland University Medical Center in Homburg and the University of the Saarland in Germany.
    • Dr. Schattenberg completed his post-doctoral training at Albert-Einstein College of Medicine in New York, focusing on signaling pathways involved in acute and chronic liver injury, particularly in metabolic dysfunction associated steatotic liver disease (MASLD).
    • He is board-certified in Internal Medicine, Gastroenterology & Hepatology, and Infectious Disease.
    • His research specializes in translational sciences and clinical trials in Hepatology, with a focus on new technologies and approaches for the prevention, screening, and treatment of metabolic liver disease.
    • Dr. Schattenberg is involved in multinational, EU-funded research consortia exploring biomarkers and novel treatment methods for liver diseases.
    • He is a member of the Policy, Public Health, and Advocacy Committee of the European Association for the Study of the Liver (EASL).
    • He serves on the Editorial Boards of “Hepatology” and “Alimentary Pharmacology & Therapeutics” and is an Associate Editor for “JHEP Reports.”

    Dr. Diana J. Leeming

    • Dr. Diana Julie Leeming is the Senior Director of Fibrosis, Hepatic, and Pulmonary Research at Nordic Bioscience.
    • She joined Nordic Bioscience in 2004 and assumed the role of Director of Fibrosis in 2010, later being promoted to Senior Director in 2024.
    • Dr. Leeming focuses on developing serologically assessed markers to evaluate extracellular matrix remodeling in patients with pulmonary or hepatic fibrosis, aiding in diagnosis and pharmacodynamic evaluation.
    • She is a principal inventor of the PRO-C3 assay, a fibrogenesis marker utilized in multiple clinical trial studies.
    • Dr. Leeming has authored over 280 peer-reviewed publications, demonstrating her extensive contributions to the field.
    • Her H-index is 61, her I10-index is 174, and her research has garnered over 11,825 citations as of March 2024.

    Dr. Morten A. Karsdal

    • Dr. Morten Karsdal joined Nordic Bioscience in 2001 and became CEO in June 2010, leading the company to significant advancements in biomarker development and disease biology.
    • Dr. Karsdal is an honorary professor of inflammation research at the University of Southern Denmark, where he continues to supervise PhD students, fostering the next generation of researchers.
    • Dr. Karsdal chairs the Extracellular Matrix Pharmacology Congress, an important forum for advancing drug development by focusing on the extracellular matrix (ECM) as a key factor in most chronic diseases. He is renowned for his deep expertise in fibrosis, rheumatology (including rheumatoid arthritis and osteoarthritis), diabetes, and other chronic conditions, particularly in relation to ECM and biomarker research.
    • Dr. Karsdal has led the development of FDA-approved and supported molecular diagnostics, as well as more than 100 commercialized biomarker assays, including ELISA assays and high precision automated platforms.
    • He has extensive experience in clinical trial design and the clinical application of biochemical markers, often serving as a consultant to major pharmaceutical companies for the use of serological biomarkers in clinical trials.
    • In 2016, he and his research team authored the first edition of “Biochemistry of Collagens, Laminins and Elastin,” published by Elsevier Science. The book, now in its 3rd edition as of 2023, is a key resource on collagens and structural proteins, with a focus on their applications in chronic diseases.

    Get in touch

    Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
    +45 4452 5252 Contact us via email!

      TGFBI Is the Local Mediator of Pathological TGF-β Activity in Pancreatic Fibroblasts

      Posted on by Claire Hornung

      Stroma-derived βigH3 (TGFBI) is the local mediator of pathological TGF-β activity in pancreatic fibroblasts and a target to treat in cancer patients with high fibrotic activity

      Introduction

      The pro-peptide of type III collagen (nordicPRO-C3™) is a circulating prognostic biomarker that can identify cancer patients with active fibrosis. Consequently, modifiers of nordicPRO-C3™ expression are potential anti-fibrotic targets for cancer. The aim was to identify genetic variants associated with circulating nordicPRO-C3™ levels and explore the relevance as pharmacological targets for treatment of fibrotic cancers.

      Poster

      ESMO2024 TGFBI_Nordic BioscienceDownload

      Conclusion

      An association between BigH3 and nordicPRO-C3™ was found by GWAS, in vitro, and in patients with PDAC: TGF-β induce BigH3, which subsequently activate fibroblasts to become fibrotic, resulting in elevated levels of nordicPRO-C3™, which in turn can be modulated by an anti-BigH3 antibody. This highlights the potential for treatment of tumor fibrosis by inhibiting BIGH3 in cancer patients with elevated nordicPRO-C3™ levels.

      Get in touch

      Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
      +45 4452 5252 Contact us via email!

        Treprostinil Reduces Fibrosis Biomarkers in the Scar-in-a-Jar Model Using a Fibrotic Cocktail

        Posted on by Claire Hornung

        Treprostinil reduces clinically relevant fibrosis biomarkers in the Scar-in-a-Jar model using a fibrotic cocktail

        Introduction

        The activation of fibroblasts and the subsequent deposition of extracellular matrix (ECM) play a pivotal role in the development of interstitial lung disease (ILD), making it crucial for novel anti-fibrotic drugs.

        In this study, we investigated the effects of a fibrotic cocktail (FC) that consists of eight pro-fibrotic and pro-inflammatory cytokines and one growth factor in the Scar-in-a-Jar fibroblast model, thereby mimicking the complex microenvironment associated with fibrotic ILDs.

        Poster

        ERS2024_Treprostinil_ScarInAJar_Nordic BioscienceDownload

        Conclusion

        The FC effectively stimulated fibrogenesis in the Scar-in-a-Jar in-vitro model, leading to elevated
        levels of the fibrosis biomarkers nordicPRO-C3™, nordicPRO-C6™ and FBN-C™. Treprostinil significantly inhibited fibrogenesis and collagen deposition quantified by ELISA. In conclusion, the Scar-in-a-Jar model is a useful tool for screening novel anti-fibrotic drugs.

        Get in touch

        Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
        +45 4452 5252 Contact us via email!

          ELP-3 as a Potential Serological Biomarker to Distinguish Fibrotic from Non-Fibrotic HP

          Posted on by Claire Hornung

          A specific elastin fragment (ELP-3) as a potential serological biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis

          Introduction

          Hypersensitivity Pneumonitis (HP) is defined by an exaggerated immune response to antigens that may develop into pulmonary fibrosis. Elastin, a structural lung protein, is susceptible to degradation by activated neutrophils during inflammation via proteinase-3. This process releases elastin fragments into circulation that can be quantified by the ELP-3 assay.

          This study aimed to evaluate serum ELP-3 in HP and compare it with healthy, IPF and chronic obstructive pulmonary disease (COPD).

          Poster

          ERS2024_ELP3_HP_Nordic BioscienceDownload

          Conclusion

          The serum ELP-3 is elevated in patients with different chronic lung diseases, particularly in HP. Notably, ELP-3 was able to separate non-fibrotic from fibrotic HP patients. These findings highlight the potential value of ELP-3 as a biomarker that provides additional clinical information beyond conventional inflammation markers.

          Get in touch

          Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
          +45 4452 5252 Contact us via email!

            CC16-HNE Is Associated with Mortality and Pulmonary Hypertension in IPF

            Posted on by Claire Hornung

            A marker of human neutrophil elastase mediated club cell secretary protein-16 degradation in (CC16-HNE) is associated with mortality and pulmonary hypertension in idiopathic pulmonary fibrosis

            Introduction

            Idiopathic pulmonary fibrosis (IPF) is characterized by epithelial injury, fibrosis, and an aberrant immune response. Club cells are essential for lung homeostasis by repairing the injured epithelium and secreting the anti-inflammatory club cell secretory protein-16 (CC16). Additionally, activated neutrophils release human neutrophil elastase (HNE) during inflammation. Our aim was to investigate if serum measurements of CC16 degradation by HNE (CC16-HNE) were related to IPF mortality and pulmonary hypertension (PH).

            Poster

            ERS2024_CC16HNE_Mortality_IPF_Nordic BioscienceDownload

            Conclusion

            Low serum CC16-HNE at baseline was associated with increased risk of mortality and a PH complication in IPF. These results indicate that a neutrophil immune response and degradation of CC16 is relevant for disease outcome. CC16 degradation by HNE could serve as a prognostic biomarker for IPF and diagnostic for a PH complication.

            Get in touch

            Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
            +45 4452 5252 Contact us via email!

              Prolonged Inflammation of Fibroblasts Promotes Formation of Type III Collagen and Fibronectin

              Posted on by Claire Hornung

              Prolonged inflammatory stimulation of fibroblasts promotes the formation of type III collagen and fibronectin in response to TGF-β1

              Introduction

              Inflammation is associated with tissue damage and the concomitant induction of wound healing responses. Pro-inflammatory cytokines such as TNF-α initiate wound healing by promoting the activation and proliferation of fibroblasts. Growth factors such as TGF-β1 drive granulation tissue formation, a type of new connective tissue formed by fibroblasts during wound healing. Fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA) identify distinct fibroblast phenotypes associated with distinct ECM remodeling.

              In this study we investigated whether prolonged inflammatory stimulation of fibroblasts would augment the fibrogenic response to TGF-β1, and the fibroblast phenotype resulting from fibro-inflammation.

              Poster

              ECM2024 TGF-β1_Nordic BioscienceDownload

              Conclusion

              TNF-α shifts TGF-β1 stimulated α-SMA+ fibroblasts towards a fibro-inflammatory FAP+ phenotype. The TGF-β1 + TNF-α stimulation is characterized by increased type III collagen and fibronectin formation, while type I and VI collagen are reduced, compared to TGF-β1 stimulation only. In conclusion, the soluble nordicPRO-C3™ and FBN-C biomarkers may be used to identify FAP + fibroblast activity, associated with fibrogenesis.

              Get in touch

              Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
              +45 4452 5252 Contact us via email!

                Biomarkers Quantifying Changes in the Hair Follicular ECM Are Elevated in Alopecia Patients

                Posted on by Claire Hornung

                Biomarkers quantifying changes in the hair follicular extracellular matrix are elevated in patients with alopecia

                Introduction

                Alterations in the extracellular matrix (ECM) within the hair follicle microenvironment may contribute to the development and progression of non-scarring alopecia. Various ECM proteins such as type III collagen
                and elastin are present within the hair follicle ECM. During wound healing, there is an increase in type III
                collagen, while elastin is responsible for the elasticity of connective tissue, and its degradation might affect hair follicle function. There is also an increased immune cell infiltration, such as neutrophils, which target the hair bulb and disrupt the normal ECM architecture within the follicle leading to hair loss.


                We aimed to investigate if biomarkers reflecting ECM remodeling could separate patients with non-scarring alopecia from healthy controls.

                Poster

                ECM2024 Alopecia_Nordic BioscienceDownload

                Conclusion

                Patients with alopecia had an increase in type III collagen formation and elastin degradation, indicating the wound healing processes as well as the loss of elasticity within the surrounding ECM of the hair follicle. Objective biomarkers quantifying changes the hair follicle and its surrounding tissues could serve as potential biomarkers of diagnosis and disease monitoring in alopecia.

                Get in touch

                Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
                +45 4452 5252 Contact us via email!

                  PRO-C22 Is Associated with Disease Severity, Activity, and Systemic Inflammation in HS

                  Posted on by Claire Hornung

                  PRO-C22 – A novel serological biomarker of tissue damage is associated with disease severity, disease activity, and systemic inflammation in patients with hidradenitis suppurativa

                  Introduction

                  Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a substantial diagnostic delay, in part due to diagnostic challenges with lesions mimicking abscesses. Utilizing robust serological biomarkers could aid in earlier diagnosis and better monitoring of disease severity. One such potential biomarker is type XXII collagen, a fibrillar collagen located at the interface between the anagen hair follicle and the dermis in the skin.

                  In this study we aimed to evaluate a novel serological biomarker reflecting type XXII collagen turnover, in patients with HS to test its association with disease severity, disease activity, and systemic inflammation.

                  Poster

                  ECM2024 PRO-C22_in HS_Nordic BioscienceDownload

                  Conclusion

                  We developed and evaluated the novel biomarker PRO-C22 reflecting tissue damage, which was associated to disease severity, activity and correlated with systemic inflammation in patients with HS. Such biomarker may be useful in early patient stratification and efficacy of treatment marker.

                  Get in touch

                  Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
                  +45 4452 5252 Contact us via email!

                    FAP Activity Is Reflected by a Specific Fragment of Type III Collagen

                    Posted on by Claire Hornung

                    The activity of fibroblast activation protein (FAP) is reflected by a specific fragment of type III collagen that can be serologically assessed and serve as a non-invasive biomarker

                    Introduction

                    Non-small cell lung cancers (NSCLC) are associated with both inflammatory and fibrotic tumor microenvironments (TME). The inflammatory component involves an influx of macrophages, which release matrix metalloproteinases (MMPs) that cleave extracellular matrix proteins, including type III collagen, leading to the release of the C3M fragment into circulation. In parallel, tumor fibrosis is marked by the accumulation of fibroblasts and high expression of Fibroblast Activation Protein (FAP), which is typically low or absent in benign tissue. FAP possesses unique proteolytic activity and has been shown to cleave various ECM proteins, including collagens.

                    Based on this, we hypothesized that FAP-mediated cleavage of type III collagen would generate a distinct fragment, C3F, that could enter the circulation and serve as a potential marker of FAP activity within the TME.

                    Poster

                    ECM2024_RAP_Nordic BioscienceDownload

                    Conclusion

                    FAP activity can be assessed by targeting a FAP-cleaved fragment of type III collagen, C3F and function as a non-invasive biomarker for patients with NSCLC. By showing that this fragment differs from the MMP-generated fragment C3M, this study supports the notion that different biological processes are reflected in the proteolytic degradation of the ECM and can be reflected by specific circulating protein fragments.

                    Get in touch

                    Are you interested in exploring collaboration possibilities?
Enter your information in the form and a representative will contact you shortly.
                    +45 4452 5252 Contact us via email!