Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells

Zhang,Yunyuan; Chen,Xian; Qiao,Min; Zhang,Bing-Qiang; Wang,Ning; Zhang,Zhonglin; Liao,Zhan; Zeng,Liyi; Deng,Youlin; Deng,Fang; Zhang,Junhui; Yin,Liangjun; Liu,Wei; Zhang,Qian; Ya,Zhengjian; Ye,Jixing; Wang,Zhongliang; Zhou,Lan; Luu,Hue  H.; Haydon,Rex  C.; He,Tong-Chuan; Zhang,Hongyu

doi:10.3892/or.2014.3308

Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells

Authors:
- Yunyuan Zhang
- Xian Chen
- Min Qiao
- Bing-Qiang Zhang
- Ning Wang
- Zhonglin Zhang
- Zhan Liao
- Liyi Zeng
- Youlin Deng
- Fang Deng
- Junhui Zhang
- Liangjun Yin
- Wei Liu
- Qian Zhang
- Zhengjian Ya
- Jixing Ye
- Zhongliang Wang
- Lan Zhou
- Hue H. Luu
- Rex C. Haydon
- Tong-Chuan He
- Hongyu Zhang
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Affiliations: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China, Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA
Published online on: July 3, 2014 https://doi.org/10.3892/or.2014.3308
Pages: 1013-1020

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Abstract

Colorectal cancer (CRC) is one of the most deadly cancers worldwide. Significant progress has been made in understanding the molecular pathogenesis of CRC, which has led to successful early diagnosis, surgical intervention and combination chemotherapy. However, limited therapeutic options are available for metastatic and/or drug-resistant CRC. While the aberrantly activated Wnt/β-catenin pathway plays a critical initiating role in CRC development, disruption of the bone morphogenetic protein (BMP) pathway causes juvenile polyposis syndrome, suggesting that BMP signaling may play a role in CRC development. However, conflicting results have been reported concerning the possible roles of BMP signaling in sporadic colon cancer. Here, we investigated the effect of BMP2 on the proliferation, migration, invasiveness and tumor growth capability of human CRC cells. Using an adenovirus vector that overexpresses BMP2 and the piggyBac transposon-mediated stable BMP2 overexpression CRC line, we found that exogenous BMP2 effectively inhibited HCT116 cell proliferation and colony formation. BMP2 was shown to suppress colon cancer cell migration and invasiveness. Under a low serum culture condition, forced expression of BMP2 induced a significantly increased level of apoptosis in HCT116 cells. Using a xenograft tumor model, we found that forced expression of BMP2 in HCT116 cells suppressed tumor growth, accompanied by decreased cell proliferation activity. Taken together, our results strongly suggest that BMP2 plays an important inhibitory role in governing the proliferation and aggressive features of human CRC cells.

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