The roles of platelet GPIIb/IIIa and alphavbeta3 integrins during HeLa cells adhesion, migration, and invasion to monolayer endothelium under static and dynamic shear flow.
During their passage through the circulatory system, tumor cells undergo extensive interactions with various host cells including endothelial cells and platelets. Mechanisms mediating tumor cell adhesion, migration, and metastasis to vessel wall under flow condition are largely unknown. The aim of this study was to investigate the potential roles of GPIIb/IIIa and alphavbeta3 integrins underlying the HeLa-endothelium interaction in static and dynamic flow conditions. HeLa cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of transmigrated or invaded HeLa cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of alphavbeta3 integrin, also inhibited HeLa cell transmigration. Interestingly, the presence of endothelial cells had significant effect on HeLa cell migration regardless of static or cocultured flow condition. The adhesion capability of HeLa cells to endothelial monolayer was also significantly affected by GPIIb/IIIa and alphavbeta3 integrins. The arrested HeLa cells increased nearly 5-fold in the presence of thrombin-activated platelets at shear stress condition (1.84 dyn/cm(2) exposure for 1 hour) than the control (static). Our findings showed that GPIIb/IIIa and alphavbeta3 integrins are important mediators in the pathology of cervical cancer and provide a molecular basis for the future therapy, and the efficient antitumor benefit should target multiple receptors on tumor cells and platelets.
Liu
Yiyao
Y
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. liuyiyao@hotmail.com
Zhao
Fenglong
F
Gu
Wentian
W
Yang
Haishiu
H
Meng
Quoquan
Q
Zhang
Yunxiang
Y
Yang
Hong
H
Duan
Qi
Q
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000077542:Eptifibatide; D006367:HeLa Cells; D018056:Hemorheology / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013314:Stress, Mechanical; D013917:Thrombin / Q000494:pharmacology
D039302:Integrin alphaVbeta3; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin; D000077542:Eptifibatide