title: Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells.
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.
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yunyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Qiao
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Bing-Qiang
authors.initials: BQ
authors.lastname: Zhang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Liao
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Liyi
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Youlin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liangjun
authors.initials: L
authors.lastname: Yin
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhengjian
authors.initials: Z
authors.lastname: Ya
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Jixing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.affiliation: Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.affiliation: Ministry of Education Key Laboratory of Clinical Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2