Role of integrins in invasion of endometrial cancer cell lines.
OBJECTIVE
The objective of this study was to determine whether there is a link between integrins and components of the plasminogen system, regarding tumor cell invasion to the artificial extracellular matrix.


METHODS
Immunocytochemistry was performed with antibodies directed against integrins alpha2beta1, alpha4beta1, alpha5beta1, alpha6beta1, and alpha(nu)beta3 Cell adhesion was studied by cell attachment to matrix proteins. Integrin-mediated migration of cells into the artificial matrix was studied in an invasion assay. Last, immunoreactivity of the components of the plasminogen system was estimated by ELISA.


RESULTS
HEC-1A, Ishikawa, and AN3CA cell lines express the alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1 integrins. Adhesion of cells to fibronectin and laminin was inhibited by monoclonal antibodies directed against appropriate integrin subunits. Migration into the matrigel was partially blocked with mAbs to alpha4beta1 as well as alpha5beta1, alpha6beta1 integrins and their combination. No differences in either uPA or PAI-1 immunoreactivity were found after addition of the mAbs.


CONCLUSIONS
Alpha4beta1, alpha5beta1, and alpha6beta1 heterodimers mediate adhesion as well as migration into the artificial matrix matrigel of endometrial tumor cell lines. A cooperative signaling between these integrins and uPA or its inhibitor in modulation of in vitro cell invasion is rather unprobable.
Prifti
Sophia
S
Department of Obstetrics and Gynaecology, Division of Gynecological Endocrinology and Reproductive Medicine, Ruprechts-Karls-Universität, Voss-Strasse 9, Heidelberg, 69115, Germany. sophia_prifti@med.uni-heidelberg.de
Zourab
Yaser
Y
Koumouridis
Antonios
A
Bohlmann
Michael
M
Strowitzki
Thomas
T
Rabe
Thomas
T
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator