The interplay between a fibrotic ECM and lung cancer cell behavior

<bold>Background:</bold> Fibrosis can be the result of an excessive extracellular matrix (ECM) deposition in response to TGF-β1 as a prominent profibrotic cytokine in IPF. One-third of lung cancer patients have Idiopathic pulmonary fibrosis (IPF), and this increased prevalence of lung cancer in IPF patients is not fully understood. <bold>Aims and objectives:</bold> However, the interplay between a fibrotic ECM and lung cancer cell behavior is not fully elucidated and may propose a therapeutic approach for lung cancer patients with pre-existing IPF. <bold>Methods:</bold> Epithelial-derived native ECM produced in response to TGF stimulation was used as an in vitro IPF model in BEAS2B and A549 cell lines. After decellularization, exemplar cell lines from lung cancer (NCI-H358, NCI-H1573, and NCI-H520) were grown on the intact epithelial-derived ECM. ECM remodeling, proliferation, and attachment of cancer cells were assessed. <bold>Results:</bold> As expected, the fibrotic ECM contained more ECM moieties, e.g., Fibronectin and Col IV, from both BEAS2B and A549 cells. The proliferation of NCI-H358 on BEAS2B and A549 TGF-treated derived ECM was reduced (p values 0.0041 and 0.0051, respectively). However, the reduced proliferation of NCI-H520 was not statistically significant. The attachment assay results were consistent with the proliferation assay. <bold>Conclusions:</bold> The fibrotic ECM hindered the attachment and proliferation of NCI-H358 and NCI-H520 lung cancer cells but not NCI-H1573. This may mean slower progression in bronchioloalveolar carcinoma (NCI-H358) and squamous cell carcinoma (NCI-H520) in patients with IPF. Further characterization of the fibrotic ECM is needed for clarity, and its effect on chemotherapy susceptibility remains uncertain.