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Mol. Cells 2013; 36(2): 119-126

Published online August 31, 2013

https://doi.org/10.1007/s10059-013-0043-8

© The Korean Society for Molecular and Cellular Biology

Bone Morphogenetic Protein 9 Overexpression Reduces Osteosarcoma Cell Migration and Invasion

Zilan Lv, Dandan Yang, Jie Li, Min Hu, Min Luo, Xiaoqin Zhan, Peipei Song, Chen Liu, Huili Bai, Baolin Li, Yang Yang, Yingying Chen, Qiong Shi, and Yaguang Weng

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education and School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of China

Received: February 7, 2013; Revised: May 8, 2013; Accepted: May 24, 2013

Abstract

Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent
pathway by downregulating the expression and activity of MMP9.

Keywords BMP9, invasion, migration, MMP9, osteosarcoma

Article

Research Article

Mol. Cells 2013; 36(2): 119-126

Published online August 31, 2013 https://doi.org/10.1007/s10059-013-0043-8

Copyright © The Korean Society for Molecular and Cellular Biology.

Bone Morphogenetic Protein 9 Overexpression Reduces Osteosarcoma Cell Migration and Invasion

Zilan Lv, Dandan Yang, Jie Li, Min Hu, Min Luo, Xiaoqin Zhan, Peipei Song, Chen Liu, Huili Bai, Baolin Li, Yang Yang, Yingying Chen, Qiong Shi, and Yaguang Weng

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education and School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of China

Received: February 7, 2013; Revised: May 8, 2013; Accepted: May 24, 2013

Abstract

Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent
pathway by downregulating the expression and activity of MMP9.

Keywords: BMP9, invasion, migration, MMP9, osteosarcoma

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

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