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vß3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially
Department of Obstetrics and Gynecology (K.B.C.A.R., M.A.F., W.R.M., P.R.T., B.A.L.), Division of Reproductive Endocrinology and Infertility, University of North Carolina, Chapel Hill, North Carolina 27599; Kaiser Permanente (M.J.M.), Department of Obstetrics and Gynecology, Sacramento, California 95815-4807; and London Regional Cancer Centre and Department of Oncology (A.F.C.), University of Western Ontario, London, Ontario, Canada N6A 4L6
Address all correspondence and requests for reprints to: Dr. Bruce A. Lessey, Department of Obstetrics and Gynecology, The University of North Carolina at Chapel Hill, MacNider Building, CB 7570, Chapel Hill, North Carolina 27599. E-mail: lessey{at}med.unc.edu
Abstract
Osteopontin is an arginine-glycine-aspartic acid-containing acidic
glycoprotein component of the extracellular matrix that is postulated
to bind to integrin receptors at the cell surface to mediate cellular
adhesion and migration during embryo implantation. The primary aim of
this study was to examine the uterine expression of osteopontin
throughout the menstrual cycle in normal fertile controls sampled
prospectively based on urinary LH surge detection. Expression of
osteopontin was documented using Northern blot analysis, in
situ hybridization, and immunohistochemistry. Furthermore, the
temporal pattern of osteopontin expression was compared with that of
its receptor, the 
vß3 integrin. Using Ishikawa cells, a well
differentiated endometrial adenocarcinoma cell line, the in
vitro regulation of osteopontin and its receptor vß3
integrin was studied. By Northern blot analysis, osteopontin mRNA
appears during the early secretory phase, with maximal expression
occurring in mid to late secretory-phase endometrium. The in
situ hybridization analyses showed that osteopontin mRNA
specifically localized in epithelial cells within the endometrium.
Immunostaining of osteopontin was detected in the glandular secretions
and on the apical portions of surface (luminal) epithelium. The
patterns of expression of osteopontin by Northern blotting, in
situ hybridization, and immunohistochemistry are remarkably
similar to the pattern for the vß3 integrin. Despite these
similarities in distribution, in vitro studies
demonstrate that osteopontin and ß3 integrin subunit expression are
differentially regulated. The expression of osteopontin was primarily
induced in response to progesterone, whereas the ß3 integrin subunit
was up-regulated by epidermal growth factor or heparin-binding
epidermal growth factor. The differential regulation of these two
endometrial proteins suggests the existence of two separate pathways
regulating epithelial gene expression in human endometrium during the
window of implantation. In adhesion assays using Ishikawa cells,
vß3 but not vß5 or ß1 integrins appear to be the primary
receptors for osteopontin. These findings may better define the factors
that favor the development of a receptive endometrium.
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