title: Laminin-332 and α3β1 integrin-supported migration of bronchial epithelial cells is modulated by fibronectin.
abstract: The repair of the bronchiolar epithelium damaged by cell-mediated, physical, or chemical insult requires epithelial cell migration over a provisional matrix composed of complexes of extracellular matrix molecules, including fibronectin and laminin. These matrix molecules support migration and enhance cell adhesion. When cells adhere too tightly to their matrix they fail to move; but if they adhere too little, they are unable to develop the traction force necessary for motility. Thus, we investigated the relative contributions of laminin and fibronectin to bronchiolar cell adhesion and migration using the immortalized bronchial lung epithelial cell line (BEP2D) and normal human bronchial epithelial (NHBE) cells, both of which assemble a laminin α3β3γ2 (LM332)/fibronectin-rich matrix. Intriguingly, BEP2D and NHBE cells migrate significantly faster on an LM332-rich matrix than on fibronectin. Moreover, addition of fibronectin to LM332 matrix suppresses motility of both cell types. Finally, fibronectin enhances the adhesion of both BEP2D and NHBE cells to LM332-coated surfaces. These results suggest that fibronectin fine tunes LM332-mediated migration by boosting bronchiolar cell adhesion to substrate. We suggest that, during epithelial wound healing of the injured airway, fibronectin plays an important adhesive role for laminin-driven epithelial cell motility by promoting a stable cellular interaction with the provisional matrix.
authors.affiliation: 1 Department of Cell and Molecular Biology and Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kligys
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Wu
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hamill
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Lewandowski
authors.forename: Susan B
authors.initials: SB
authors.lastname: Hopkinson
authors.forename: G R Scott
authors.initials: GR
authors.lastname: Budinger
authors.forename: Jonathan C R
authors.initials: JC
authors.lastname: Jones
mesh_terms: D001980:Bronchi / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020545:Respiratory Mucosa / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D014945:Wound Healing; D000097794:Kalinin
chemical_list: D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039201:Integrin alpha3beta1; D039503:Integrin alpha6; D000097794:Kalinin