title: Activated platelets interact with lung cancer cells through P-selectin glycoprotein ligand-1.
abstract: Hematogenous metastasis always leads to the poor prognosis of non-small cell lung cancers (NSCLC). Activated platelets are involved in hematogenous metastasis and may be a potential therapeutic target. P-selectin is an important adhesion molecule and expressed on the surface of activated platelets. P-selectin glycoprotein ligand-1 (PSGL-1) as a transmembrane protein is expressed on the surface of various cell types. P-selectin can bind to PSGL-1, and thereby initiate the platelet-mediated cell adhesion. The aim of the study was to investigate the degree of platelet activation in NSCLC and the roles of PSGL-1 in the activation of platelets. Purified platelets were obtained from NSCLC patients (40 lung adenocarcinomas and 26 lung squamous cell carcinomas), and P-selectin expression was detected by fluorescence-activated cell sorter. The population of peripheral blood platelets with P-selectin expression in lung adenocarcinoma was 63.16 ± 25.44 %, and significantly higher than that in lung squamous cell carcinoma (35.97 ± 17.19 %) and the healthy population (9.12 ± 7.66 %, n = 30). A specific small hairpin RNA (shRNA) for PSGL-1 was transfected into A549 human alveolar cell carcinoma cells. The expressions of PSGL-1 mRNA and protein were significantly reduced with the PSGL-1 shRNA (p < 0.01). Furthermore, the knockdown of PSGL-1 also resulted in the significantly reduced aggregate formation of activated platelets and A549 cells. Thus, activated platelets may interact with lung cancer cells through PSGL-1. Inhibiting platelet activation and/or down-regulating PSGL-1 expression may be useful for suppression of tumor metastasis.
authors.affiliation: Department of Respiratory diseases, Southwest Hospital, the Third Military Medical University, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gong
authors.forename: Yun
authors.initials: Y
authors.lastname: Cai
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Heping
authors.initials: H
authors.lastname: Yang
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015539:Platelet Activation / Q000502:physiology*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D034741:RNA, Small Interfering