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Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary research

Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells

Authors: Radhakrishnan Vishnubalaji, Shijun Yue, Musaad Alfayez, Moustapha Kassem, Fei-Fei Liu, Abdullah Aldahmash, Nehad M. Alajez

Published in: Cancer Cell International | Issue 1/2016

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Abstract

Background

Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised.

Methods

Bioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice.

Results

Our data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice.

Conclusions

Our data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC.
Appendix
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Literature
1.
Khan K, Wale A, Brown G, Chau I. Colorectal cancer with liver metastases: neoadjuvant chemotherapy, surgical resection first or palliation alone? World J Gastroenterol. 2014;20(35):12391–406.CrossRefPubMedPubMedCentral
2.
Vishnubalaji R, Hamam R, Abdulla MH, Mohammed MA, Kassem M, Al-Obeed O, Aldahmash A, Alajez NM. Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer. Cell Death Dis. 2015;6:e1614.CrossRefPubMedPubMedCentral
3.
Alajez NM. Significance of BMI1 and FSCN1 expression in colorectal cancer. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 2016;22(4):288–93.CrossRef
4.
5.
Hardwick JC, Kodach LL, Offerhaus GJ, van den Brink GR. Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer. 2008;8(10):806–12.CrossRefPubMed
6.
Augeri DJ, Langenfeld E, Castle M, Gilleran JA, Langenfeld J. Inhibition of BMP and of TGFbeta receptors downregulates expression of XIAP and TAK1 leading to lung cancer cell death. Mol Cancer. 2016;15(1):27.CrossRefPubMedPubMedCentral
7.
Bami M, Mavrogenis AF, Angelini A, Milonaki M, Mitsiokapa E, Stamoulis D, Soucacos PN. Bone morphogenetic protein signaling in musculoskeletal cancer. J Cancer Res Clin Oncol. 2016;142: 2061–72.CrossRefPubMed
8.
Hardwick JC, Van Den Brink GR, Bleuming SA, Ballester I, Van Den Brande JM, Keller JJ, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Gastroenterology. 2004;126(1):111–21.CrossRefPubMed
9.
Loh K, Chia JA, Greco S, Cozzi SJ, Buttenshaw RL, Bond CE, Simms LA, Pike T, Young JP, Jass JR, et al. Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development. Genes Chromosomes Cancer. 2008;47(6):449–60.CrossRefPubMed
10.
Beck SE, Jung BH, Fiorino A, Gomez J, Rosario ED, Cabrera BL, Huang SC, Chow JY, Carethers JM. Bone morphogenetic protein signalling and growth suppression in colon cancer. Am J Physiol Gastrointest Liver Physiol. 2006;291(1):G135–45.CrossRefPubMedPubMedCentral
11.
Ali D, Hamam R, Alfayez M, Kassem M, Aldahmash A, Alajez NM. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells. Stem Cells Transl Med. 2016;5(8):1036–47.CrossRefPubMed
12.
Vishnubalaji R, Hamam R, Yue S, Al-Obeed O, Kassem M, Liu FF, Aldahmash A, Alajez NM. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1. Oncotarget. 2016;7(24):35789–802.
13.
Ito E, Yue S, Moriyama EH, Hui AB, Kim I, Shi W, Alajez NM, Bhogal N, Li G, Datti A, et al. Uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer. Sci Transl Med. 2011; 3(67):67ra67.
14.
Al-toub M, Almusa A, Almajed M, Al-Nbaheen M, Kassem M, Aldahmash A, Alajez NM. Pleiotropic effects of cancer cells’ secreted factors on human stromal (mesenchymal) stem cells. Stem Cell Res Ther. 2013;4(5):114.CrossRefPubMedPubMedCentral
15.
Alajez NM, Lenarduzzi M, Ito E, Hui AB, Shi W, Bruce J, Yue S, Huang SH, Xu W, Waldron J, et al. MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. Cancer Res. 2011;71(6):2381–91.CrossRefPubMed
16.
Zhang Y, Chen X, Qiao M, Zhang BQ, Wang N, Zhang Z, Liao Z, Zeng L, Deng Y, Deng F, et al. Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells. Oncol Rep. 2014;32(3):1013–20.PubMedPubMedCentral
17.
Gordon KJ, Blobe GC. Role of transforming growth factor-beta superfamily signaling pathways in human disease. Biochim Biophys Acta. 2008;1782(4):197–228.CrossRefPubMed
18.
Alarmo EL, Parssinen J, Ketolainen JM, Savinainen K, Karhu R, Kallioniemi A. BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer Lett. 2009;275(1):35–43.CrossRefPubMed
Metadata
Title
Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells
Authors
Radhakrishnan Vishnubalaji
Shijun Yue
Musaad Alfayez
Moustapha Kassem
Fei-Fei Liu
Abdullah Aldahmash
Nehad M. Alajez
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0355-9

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