The Effects of Calcium, Epidermal Growth Factor and Retinoic Acid on A9/ α6 β4 Integrin Expression of Normal and Malignant Keratoinocytes In Vitro
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Authors
Reinke, Timothy S.
Issue Date
1991
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Monoclonal antibody UM-A9 defines the α6 4β intergrin
associated with aggressive human squamous carcinomas (Van
Waes et al.) 1991) .
A9 antigen was found to be selectively expressed on
only the basal surface of normal keratinocytes in culture
while some squamous carcinoma cell lines express more
A9/ α6 4β antigen. Where both primary and metastatic tumor
cells lines were established from the same patient, the
metastatic tumors expressed more A9/ α6 4β antigen than the
primary, with expression on the basal as well apical
surfaces (Carey et al. 1990). These observations suggest an
association of A9/ α6 4β expression and biological behavior of
malignancy (Kimmel and Carey 1986) .
High expression of A9 antigen on patient's tumors grown
in culture is associated with early relapse and death. As a
biological marker of tumor progression, A9 antigen has
predictive value in clinical behavior of tumors (Wolf et al,
1990}. Whether A9 expression functions directly in clinical
progression of squamous cancers is not yet known.
We studied morphology and A9 antigen expression on
normal and malignant keratinocytes in vitro challenged by
Epidermal Growth Factor (EGF) , Calcium (Ca++) and Retinoic
acid (RA), a growth promotional factor, an inducer of
differentiation, and an inhibitor of differentiation
respectively. We were interested in the effects of these
chemicals on α6 4β expression, in particular how normal and
malignant keratinocytes differ in expression of A9/ α6 4β when
grown in different defined medias.
Normal and malignant keratinocytes grown in the
presence of calcium showed altered morphology. For cells
grown in EGF, an increase in expression was seen. Down
regulation or polarization of the A9/ α6 4β integrin for
normal keratinocytes grown in media containing EGF plus Ca++
was seen, whereas malignant cells maintained basal as well
as apical expression of α6 4β integrin. Normal cells grown
in media containing RA without calcium down regulated
expression whereas the same cells grown in RA plus calcium
showed up regulation of A9/ α6 4β integrin. A9/ α6 4β antigen
expression on malignant keratinocytes was unchanged through
out the experiment.
Description
v, 33 p.
Citation
Publisher
Kalamazoo College
License
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