A1 Refereed original research article in a scientific journal
Different integrins mediate cell spreading, haptotaxis and lateral migration of HaCaT keratinocytes on fibronectin
Authors: Koivisto L, Larjava K, Hakkinen L, Uitto VJ, Heino J, Larjava H
Publisher: HARWOOD ACAD PUBL GMBH
Publication year: 1999
Journal: Cell Adhesion and Communication
Journal name in source: CELL ADHESION AND COMMUNICATION
Journal acronym: CELL ADHES COMMUN
Volume: 7
Issue: 3
First page : 245
Last page: 257
Number of pages: 13
ISSN: 1061-5385
DOI: https://doi.org/10.3109/15419069909010806
Abstract
Collaborative role of various fibronectin-binding integrins (alpha 5 beta 1, alpha v beta 1 and alpha v beta 6) as mediators of cell adhesion and migration on fibronectin was studied using cultured HaCaT keratinocytes. This cell line spontaneously expressed all three fibronectin-binding integrins. In addition, the expression of alpha v beta 6 integrin was strongly and specifically upregulated by transforming growth factor-beta 1 (TGF beta 1) whereas the amount of other integrins remained practically unchanged on the cell surface. Adhesion, spreading and motility of HaCaT keratinocytes on fibronectin were promoted by TGF beta 1. Based on antibody blocking experiments, both untreated and TGF beta 1-treated HaCaT cells used alpha v beta 6 integrin as their main fibronectin receptor for cell spreading. In contrast to TGF beta 1-treated cells, the untreated cells also needed alpha 5 beta 1 integrin for maximal cell spreading on fibronectin. Combinations of antibodies blocking both of these receptors totally prevented spreading of both untreated and TGF beta 1-treated cells. Haptotactic motility of individual HaCaT cells through fibronectin-coated membranes was again mainly dependent on alpha v beta 6 integrin, while alpha v beta 1 and alpha 5 beta 1 integrins played a lesser role both in untreated and TGF beta 1-treated HaCaT cells. However, unlike haptotaxis, lateral migration of HaCaT cell sheet was mainly mediated by beta 1 integrins, and alpha v beta 6 integrin showed a minor role. The migration process appeared to involve a number of beta 1 integrins that could adaptively replace each other when blocking antibodies were present. Thus, keratinocytes appear to use different fibronectin receptors for different functions, such as cell spreading, haptotaxis and lateral migration. The cells can also adapt to a situation where one receptor is unfunctional by switching to another receptor of the same ligand.
Collaborative role of various fibronectin-binding integrins (alpha 5 beta 1, alpha v beta 1 and alpha v beta 6) as mediators of cell adhesion and migration on fibronectin was studied using cultured HaCaT keratinocytes. This cell line spontaneously expressed all three fibronectin-binding integrins. In addition, the expression of alpha v beta 6 integrin was strongly and specifically upregulated by transforming growth factor-beta 1 (TGF beta 1) whereas the amount of other integrins remained practically unchanged on the cell surface. Adhesion, spreading and motility of HaCaT keratinocytes on fibronectin were promoted by TGF beta 1. Based on antibody blocking experiments, both untreated and TGF beta 1-treated HaCaT cells used alpha v beta 6 integrin as their main fibronectin receptor for cell spreading. In contrast to TGF beta 1-treated cells, the untreated cells also needed alpha 5 beta 1 integrin for maximal cell spreading on fibronectin. Combinations of antibodies blocking both of these receptors totally prevented spreading of both untreated and TGF beta 1-treated cells. Haptotactic motility of individual HaCaT cells through fibronectin-coated membranes was again mainly dependent on alpha v beta 6 integrin, while alpha v beta 1 and alpha 5 beta 1 integrins played a lesser role both in untreated and TGF beta 1-treated HaCaT cells. However, unlike haptotaxis, lateral migration of HaCaT cell sheet was mainly mediated by beta 1 integrins, and alpha v beta 6 integrin showed a minor role. The migration process appeared to involve a number of beta 1 integrins that could adaptively replace each other when blocking antibodies were present. Thus, keratinocytes appear to use different fibronectin receptors for different functions, such as cell spreading, haptotaxis and lateral migration. The cells can also adapt to a situation where one receptor is unfunctional by switching to another receptor of the same ligand.
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