P-selectin-mediated platelet activation promotes adhesion of non-small cell lung carcinoma cells on vascular endothelial cells under flow.
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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 ?3, ?5, ?1, 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 ?3, ?5, ?1, 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 ?3, ?5, ?1 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.
SUBMITTER: Gong L
PROVIDER: S-EPMC3493105 | biostudies-literature | 2012 Apr
REPOSITORIES: biostudies-literature
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