Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders

Autor: Signe Holm Nielsen, Nicholas Willumsen, Diana Julie Leeming, Samuel Joseph Daniels, Susanne Brix, Morten Asser Karsdal, Federica Genovese, Mette Juul Nielsen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Translational Oncology, Vol 12, Iss 2, Pp 368-374 (2019)
Druh dokumentu: article
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
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