MGr1-Ag promotes invasion and bone metastasis of small-cell lung cancer in vitro and in vivo

Zhang,Feng; Wang,Yanxia; Xu,Min; Dong,Haiying; Liu,Na; Zhou,Jing; Pang,Hailin; Ma,Ningqiang; Zhang,Ning; Pei,Yanlin; Zhang,Helong; Liu,Lili

doi:10.3892/or.2013.2396

MGr1-Ag promotes invasion and bone metastasis of small-cell lung cancer in vitro and in vivo

Authors:
- Feng Zhang
- Yanxia Wang
- Min Xu
- Haiying Dong
- Na Liu
- Jing Zhou
- Hailin Pang
- Ningqiang Ma
- Ning Zhang
- Yanlin Pei
- Helong Zhang
- Lili Liu
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Affiliations: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, P.R. China, Department of Pathology and Pathophysiology, The Fourth Military Medical University, Xi'an 710032, P.R. China
Published online on: April 9, 2013 https://doi.org/10.3892/or.2013.2396
Pages: 2283-2290

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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.

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