Invasive bronchial fibroblasts derived from asthmatic patients activate lung cancer A549 cells in�vitro

Abstract

Epidemiological data suggests that there are functional links between bronchial asthma and lung carcinogenesis. Bronchial fibroblasts serve a prominent role in the asthmatic process; however, their involvement in lung cancer progression remains unaddressed. To estimate the effect of the asthmatic microenvironment on the invasiveness of lung cancer cells, the present study compared the behavior of human non-small cell lung cancer A549 cells exposed to the signals from human bronchial fibroblasts (HBFs) derived from non-asthmatic donors (NA HBFs) and from asthmatic patients (AS HBFs). NA HBFs did not significantly affect A549 motility, whereas AS HBFs and the media conditioned with AS HBF/A549 co-cultures increased Snail-1/connexin43 expression and motility of A549 cells. In contrast to NA HBFs, which formed A549-impenetrable lateral barriers, α-SMA+ AS HBFs actively infiltrated A549 monolayers and secreted chemotactic factors that arrested A549 cells within AS HBF/A549 contact zone. However, small sub-populations of A549 cells could release from this arrest and colonize distant regions of AS HBF monolayers. These data indicated that the interactions between lung cancer cells and HBFs in asthmatic bronchi may facilitate the colonization of lung tumors by fibroblasts. It further stabilizes the tumor microenvironment and potentially facilitates collective colonization of novel bronchial loci by cancer cells. Potential mechanistic links between the asthmatic process and lung cancer progression suggest that bronchial asthma should be included in the list of potential prognostic markers for lung cancer therapy.

Helicobacter pylori‐activated gastric fibroblasts induce epithelial‐mesenchymal transition of gastric epithelial cells in vitro in a TGF‐β‐dependent manner

“…Close associations of GC with the growth factor‐producing activity of organ‐specific fibroblasts have already been reported . Numerous reports indicate that this kind of reactions is common for cancer‐predisposed fibroblasts . Notably, in our experimental model the expression of Snail mRNA was upregulated in Hp ‐infected fibroblasts.…”

“…Different clinical outcomes of Hp infection are related to differences in the patterns of impaired balance between aggressive bacterial and host defensive factors . The origin of cancers, including GC, has recently been ascribed to the disturbed cooperation between the cells and their niches, mediated by the pro‐inflammatory stimuli . Connective tissue cells, such as fibroblasts, may serve as the primary although underestimated targets of such stimuli in numerous inflammatory diseases.…”

Tumor‐Associated Protrusion Fluctuations as a Signature of Cancer Invasiveness

“…In contrast, the complex native TME comprises host tumor and a diverse repertoire of stromal cells, including immune system cells, mesenchymal stem cells, adipocytes, endothelial cells, or fibroblasts, which synergistically interact with the primary tumor. [36,37] A single cell type was chosen because we aimed to provide a simplistic framework to quantitatively/qualitatively obtain evidences on how protrusion fluctuations regulate tumor invasiveness. The influence of other cell types in the modulation of such fluctuations may need to be assessed; this will help mimicking the physiological scenario in a more realistic manner.…”

Porous Polymeric Microspheres With Controllable Pore Diameters for Tissue Engineered Lung Tumor Model Development

“…It has been reported that the interplay of malignant and non-malignant cells in the tumor microenvironment has a major effect on cancer dynamics. In particular, fibroblasts have been reported to stimulate invasive behavior and metastasic activities of A549 both on 2D and on collagen-coated matrices (Ryszawy et al, 2018;Miyazaki et al, 2019). A549 also exhibited greater drug resistance with more DNA repair potential in the presence of WI-38 fibroblasts (Kobayashi et al, 2017).…”