title: MGr1-Ag promotes invasion and bone metastasis of small-cell lung cancer in vitro and in vivo.
abstract: Bone metastasis of small-cell lung cancer (SCLC) usually occurs early in the progression of the disease. However, the molecular mechanism underlying bone metastasis is largely unknown. MGr1-Ag, a multifunction protein, has been suggested to play important roles in cell growth, differentiation and migration. In our present study, MGr1-Ag was found to be highly expressed in bone-metastatic SCLC cells (SBC-5 cell line) as compared with the expression in cells without bone-metastatic ability (SBC-3 cell line). Therefore, we hypothesized that MGr1-Ag is involved in bone metastasis of SCLC. Using a sense vector to upregulate MGr1-Ag expression in SBC-3 cells, we found that forced overexpression of MGr1-Ag enhanced cell invasion and migration in vitro and promoted bone metastases in vivo. Furthermore, specific siRNA-induced knockdown of MGr1-Ag expression in SBC-5 cells suppressed the potential of cell invasion and migration in vitro and dramatically decreased the number and sites of bone metastasis in vivo. We also found that MGr1-Ag induced SCLC cells to undergo epithelial-mesenchymal transition (EMT), as demonstrated by cell morphological changes, decreased expression of epithelial markers and increased expression of mesenchymal markers. Taken together, we conclude that MGr1-Ag promotes SCLC cell invasion and bone metastasis in vitro and in vivo, and that this is partially mediated via the EMT pathway.
authors.affiliation: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Haiying
authors.initials: H
authors.lastname: Dong
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Hailin
authors.initials: H
authors.lastname: Pang
authors.forename: Ningqiang
authors.initials: N
authors.lastname: Ma
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Pei
authors.forename: Helong
authors.initials: H
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000556:secondary; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C513384:CDH1 protein, human; D015820:Cadherins; D005353:Fibronectins; C470229:MGr1-antigen, human; D034741:RNA, Small Interfering