title: P-selectin-mediated platelet activation promotes adhesion of non-small             cell lung carcinoma cells on vascular endothelial cells under flow.
abstract: Lung cancer is a severe disease threatening human health worldwide. Distant             hematogenous metastasis results in poor prognosis and death of lung cancer patients.             In the present study, we investigated the effect of circulatory platelets (PLTs)             on hematogenous metastasis of non-small cell lung carcinoma (NSCLC). Laser scanning             confocal microscopy was employed to assay the expression of P-selectin in lung             cancer tissue, paracancerous tissue and distant tissue, respectively. Meanwhile,             fluorescence-activated cell sorting (FACS) was used to determine P-selectin activation             in peripheral blood. Purified PLTs were co-cultured with A549 cells and human             vascular endothelial cells (HuvECs). Subsequently, the formation of PLT-lung cancer             cell complexes and their effects on rolling and adhesion of A549 on the surface             of vascular endothelium were assayed. Integrin α3, α5, β1, ICAM-1 and VCAM-1 mRNAs             and proteins were measured by reverse RT-PCR and western blot analysis, respectively.             The expression of P-selectin in lung adenocarcinoma tissue was significantly stronger             compared to that in paracancerous and distant tissues. P-selectin activation in             peripheral blood in lung adenocarcinoma was markedly enhanced. The rolling rate             of A549 on HuvECs was significantly slowed down after co-culture of activated             PLTs and A549 cells. The mRNA and protein levels of integrin α3, α5, β1, ICAM-1             and VCAM-1 were significantly increased after the co-culture. In conclusion, the             PLT-lung cancer cell complexes protected the lung cancer cells from mechanical             injury under blood flow. Furthermore, up-regulated integrin α3, α5, β1 and endothelial             cell adhesion molecules ICAM-1 and VCAM-1 promoted the adhesion of A549 on vascular             endothelial cells, which may be responsible for hematogenous metastasis of lung             cancer.
authors.affiliation: Department of Respiration, The Southwest Hospital, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gong
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Mi
authors.forename: Hongchu
authors.initials: H
authors.lastname: Zhu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Heping
authors.initials: H
authors.lastname: Yang
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin / Q000494:pharmacology*; D015539:Platelet Activation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D039422:Integrin alpha3; D039482:Integrin alpha5; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1