title: Down-regulation of β3-integrin inhibits bone metastasis of small cell lung cancer.
abstract: Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis, but the molecular mechanism remains unclear. β3-integrin plays an important role in invasion of various kinds of tumors. Yet, its role in bone-metastasis of SCLC is still unknown. In this study, we first examined the expression of β3-integrin in SBC-5 and SBC-3 cells by real-time PCR, western blot and immunofluorescence. We found that, compared to none bone-metastatic SBC-3 cells, β3-integrin was highly expressed in SBC-5 cells, a specific bone-metastatic SCLC cells line characterized in our previous study. We next constructed β3-integrin siRNA and transfected SBC-5 cell line, and found that β3-integrin siRNA significantly down-regulated the β3-integrin mRNA level and protein expression in SBC-5 cell line. We further found that inhibition of β3-integrin significantly reduced tumor cell proliferation and induced apoptosis. In addition, the β3-integrin down-regulated cells presented significant decrease in cell adhesion, migration and invasion activity. Our results suggest the β3-integrin has an essential effect on tumor cell proliferation and progression, and may be a potential therapeutic target for the prevention of skeletal metastases of lung cancer.
authors.affiliation: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Min
authors.forename: Li-li
authors.initials: LL
authors.lastname: Liu
authors.forename: Hai-chuan
authors.initials: HC
authors.lastname: Su
authors.forename: Ying-ming
authors.initials: YM
authors.lastname: Feng
authors.forename: He-long
authors.initials: HL
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004338:Drug Combinations; D039661:Integrin beta3; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; C059485:matrigel; D003094:Collagen; C022616:thiazolyl blue