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

Yunyuan Zhang,Min Qiao,Xian Chen,Qian Zhang,Zhonglin Zhang,Jixing Ye,Wei Liu,Fang Deng,Hongyu Zhang,Junhui Zhang,Ning Wang,Zhongliang Wang,Lan Zhou,Youlin Deng,Hue H Luu,Rex C Haydon,Bingqiang Zhang ,Zhengjian Ya ,Yin Liang ,Tong‐Chuan He ,Lin Zhan ,Lijiang Zeng

doi:10.3892/or.2014.3308

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.

Highlights

Colorectal cancer (CRC) causes an average of 50,000 deaths per year in the US and has emerged as the second leading cause of cancer-related mortality in the US and worldwide [1,2]
We investigated the effect of BMP2 on the proliferation, migration, invasiveness and tumor growth capabilities of human colon cancer cells
We found that exogenous BMP2 effectively inhibited HCT116 cell proliferation and colony formation

Summary

Introduction

Colorectal cancer (CRC) causes an average of 50,000 deaths per year in the US and has emerged as the second leading cause of cancer-related mortality in the US and worldwide [1,2]. Other alternative pathways have been implicated in CRC development. One involves the formation of serrated adenomas that are associated with mutations in BRAF [6]. Another alternative pathway involves the formation of a hamartoma as a precursor lesion, which is in this last rare pathway to CRC that mutations in the bone morphogenetic protein (BMP) pathway were identified [7]

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Methods

Results