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Decreased expression of alpha3 and beta1 integrin subunits is responsible for differentiation-associated changes in cells behavior in terminally differentiated human oral keratinocytes.
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- Authors
- Issue Date
- 2002-07
- Publisher
- Taylor & Francis
- Citation
- Cell Commun Adhes 9(4):173-187
- Keywords
- Cells behavior ; differentiated human oral keratinocytes ; ECM proteins ; integrins ; signaling molecules
- Abstract
- Primary normal human oral keratinocytes (NHOKs) terminally differentiate in serial subculture.
To investigate whether this subculture-induced differentiation of NHOKs affects integrin
expression and cell-matrix interaction, we studied the expression levels of integrin subunits
and cellular response to the extracellular matrix (ECM) proteins in NHOKs at different population
doublings. The phosphorylation statuses of focal adhesion kinase (FAK), extracellular
signal regulated kinase (ERK), p38, and c-Jun amino-terminal kinase (JNK) were also determined
in NHOK cells cultured on ECM proteins, to evaluate the functions of integrins
with respect to cellular responses to ECM proteins. The expression levels of ®3 and ¯1 integrin
subunits progressively decreased in NHOKs undergoing terminal differentiation. The
ability of NHOKs to spread upon laminin and type I collagen significantly decreased in terminally
differentiated oral keratinocytes. Keratinocyte migration was significantly increased
on type I collagen for terminally differentiated NHOKs. Similar results were seen following
preincubation of rapidly proliferating NHOKs with function-blocking antibodies to ®3 or ¯1
integrin subunit. In contrast, fibronectin had no effect on cellular responses in NHOKs, which
were almost negligible in the expression levels of ®5 integrin subunits. The extent of FAK
phosphorylation in terminally differentiated NHOKs was notably lower than that of rapidly
proliferating cells, but was enhanced in terminally differentiated cells that were cultured on
type I collagen. Our results indicate that decreased expression of ®3 and ¯1 integrin subunits is
responsible for differentiation-associated changes in cells behavior in terminally differentiated
oral keratinocytes. Our data also show that the abrogation of the ®5¯1 integrin function caused
by omitting ®5 subunit is linked to the loss of a cell-fibronectin interaction in human oral
keratinocytes.
- ISSN
- 1541-9061
- Language
- English
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