Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders
| Autor: | Nicholas Willumsen, Diana Julie Leeming, Samuel Joseph Daniels, Susanne Brix, Mette Juul Nielsen, Morten A. Karsdal, Signe Holm Nielsen, Federica Genovese |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Original article Cancer Research Connective tissue lcsh:RC254-282 Extracellular matrix Lung Disorder 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine SDG 3 - Good Health and Well-being Fibrosis Medicine Fibroblast COPD business.industry Cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research business |
| Zdroj: | Holm Nielsen, S, Willumsen, N, Leeming, D J, Daniels, S J, Brix, S, Karsdal, M A, Genovese, F & Nielsen, M J 2019, ' Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders ', Translational Oncology, vol. 12, no. 2, pp. 368-374 . https://doi.org/10.1016/j.tranon.2018.11.004 Translational Oncology, Vol 12, Iss 2, Pp 368-374 (2019) Translational Oncology |
| ISSN: | 1936-5233 |
| DOI: | 10.1016/j.tranon.2018.11.004 |
| Popis: | 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 has been found to be upregulated in lung fibrosis and cancer. We evaluated the potential of α-SMA as a noninvasive biomarker of activated fibroblasts in lung fibrosis and cancer. METHODS: A monoclonal antibody was raised against the N-terminal of α-SMA, and a novel competitive enzyme-linked immunosorbent assay (ELISA) measuring α-SMA was developed and technically characterized. Levels of α-SMA were measured in the fibroblast model, “scar-in-a-jar” and in serum from patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive lung disorder (COPD) and non–small cell lung cancer (NSCLC) belonging to two different cohorts. RESULTS: The novel α-SMA assay was developed and validated as technically robust. Based on the scar-in-a-jar results, α-SMA was only present in the fibroblasts activated by TGF-β. In cohort 1, levels of α-SMA were significantly higher in IPF, COPD and NSCLC patients compared to healthy controls (P = 0.04, P = 0.001 and P CONCLUSIONS: In this study we developed and validated a robust competitive ELISA assay targeting the N-terminal of α-SMA. The level of α-SMA was upregulated when adding TGF-β indicating that α-SMA is increased in activated fibroblasts. The level of α-SMA in circulation was significantly higher in patients with IPF, COPD and NSCLC compared to healthy controls. This assay could potentially be used as a novel noninvasive serological biomarker for lung disorders by providing a surrogate measure of activated fibroblasts. |
| Databáze: | OpenAIRE |
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