title: Stretching fibroblasts remodels fibronectin and alters cancer cell migration.
abstract: Most investigations of cancer-stroma interactions have focused on biochemical signaling effects, with much less attention being paid to biophysical factors. In this study, we investigated the role of mechanical stimuli on human prostatic fibroblasts using a microfluidic platform that was adapted for our experiments and further developed for both repeatable performance among multiple assays and for compatibility with high-resolution confocal microscopy. Results show that mechanical stretching of normal tissue-associated fibroblasts (NAFs) alters the structure of secreted fibronectin. Specifically, unstretched NAFs deposit and assemble fibronectin in a random, mesh-like arrangement, while stretched NAFs produce matrix with a more organized, linearly aligned structure. Moreover, the stretched NAFs exhibited an enhanced capability for directing co-cultured cancer cell migration in a persistent manner. Furthermore, we show that stretching NAFs triggers complex biochemical signaling events through the observation of increased expression of platelet derived growth factor receptor α (PDGFRα). A comparison of these behaviors with those of cancer-associated fibroblasts (CAFs) indicates that the observed phenotypes of stretched NAFs are similar to those associated with CAFs, suggesting that mechanical stress is a critical factor in NAF activation and CAF genesis.
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: Mingfang
authors: M
authors: Ao
authors: Department of Mechanical Engineering, Vanderbilt University, Nashville, TN.
authors: Bryson M
authors: BM
authors: Brewer
authors: Department of Mechanical Engineering, Vanderbilt University, Nashville, TN.
authors: Lijie
authors: L
authors: Yang
authors: 1] Department of Cancer Biology, Vanderbilt University, Nashville, TN [2] Department of Urologic Surgery, Vanderbilt University, Nashville, TN.
authors: Omar E
authors: OE
authors: Franco Coronel
authors: 1] Department of Cancer Biology, Vanderbilt University, Nashville, TN [2] Department of Urologic Surgery, Vanderbilt University, Nashville, TN.
authors: Simon W
authors: SW
authors: Hayward
authors: 1] Department of Biological Sciences, Vanderbilt University, Nashville, TN [2] Department of Cancer Biology, Vanderbilt University, Nashville, TN.
authors: Donna J
authors: DJ
authors: Webb
authors: Department of Mechanical Engineering, Vanderbilt University, Nashville, TN.
authors: Deyu
authors: D
authors: Li
mesh_terms: D002465:Cell Movement; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D005353:Fibronectins; D009363:Neoplasm Proteins; D020797:Receptor, Platelet-Derived Growth Factor beta