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The serum bone morphogenetic protein-2 level in non-small-cell lung cancer patients

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Abstract

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily, and some studies demonstrated that BMPs enhance tumorigenesis and metastasis. The purpose of this study was to identify whether BMP-2 levels are elevated in the serum of non-small-cell lung cancer (NSCLC) patients and are associated with the stage and overall survival. Blood samples from 150 patients with NSCLC were analyzed. Also, 69 healthy volunteers were tested as control group. In NSCLC patients, whole blood was obtained before beginning any treatment modalities, and serum BMP-2 levels were quantified by commercially available ELISA kit. The NSCLC group demonstrated a significantly higher level of serum BMP-2 than the control group. (The median levels were 25.50 pg/ml for the control group and 72.23 pg/ml for the NSCLC group, P < 0.001). The median serum BMP-2 level in the advanced stage group (stage IIIb or IV) was significantly more elevated than that of the localized stage group (stage I, II, IIIa) (75.66 pg/ml and 44.36 pg/ml, P = 0.006). Patients with multiple metastatic sites (≥5) showed significantly higher level of serum BMP-2 than the patients with less than 5 metastatic sites. (79.39 pg/ml vs. 59.70 pg/ml, P = 0.013), and the median serum BMP-2 level from the patients with multiple metastatic organs (≥3) was significantly higher than that from the patients with single or two metastatic organs (<2) (89.39 pg/ml vs. 66.90 pg/ml, P = 0.001). Moreover, the patients with relatively lower BMP-2 level (≤70 pg/ml) had longer median overall survival than the patients with higher BMP-2 level (>70 pg/ml). (525 days vs. 260 days). One-year survival rate for the patients with lower BMP-2 level was also higher than that for the patients with higher BMP-2 level. (59.6% versus 40.2%, P = 0.034). The serum BMP-2 level is positively correlated with the stage and metastatic burden and maybe a probable predictor of survival in the NSCLC patients.

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References

  1. Wozney JM, et al. Novel regulators of bone formation: molecular clones and activities. Science. 1988;242:1528–34.

    Article  PubMed  CAS  Google Scholar 

  2. Sampath TK, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem. 1992;267:20352–62.

    PubMed  CAS  Google Scholar 

  3. Hogan BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev. 1996;10:1580–94.

    Article  PubMed  CAS  Google Scholar 

  4. LI M, Eriksen EF, Bunger C. Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. Bone. 1996;18:53–7.

    Article  Google Scholar 

  5. Massague J. TGFbeta signaling: receptors, transducers, and mad proteins. Cell. 1996;85:947–50.

    Article  PubMed  CAS  Google Scholar 

  6. Nissinen L, Pirila L, Heino J. Bone morphogenetic protein-2 is a regulator of cell adhesion. Exp Cell Res. 1997;230:377–85.

    Article  PubMed  CAS  Google Scholar 

  7. Hoodless PA, et al. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell. 1996;85:489–500.

    Article  PubMed  CAS  Google Scholar 

  8. Derynck R, Zhang Y, Feng XH. Smads: transcriptional activators of TGF-beta responses. Cell. 1998;95:737–40.

    Article  PubMed  CAS  Google Scholar 

  9. Cao X, Chen D. The BMP signaling and in vivo bone formation. Gene. 2005;357:1–8.

    Article  PubMed  CAS  Google Scholar 

  10. Feeley BT, et al. Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate cancer. J Bone Miner Res. 2005;20:2189–99.

    Article  PubMed  CAS  Google Scholar 

  11. Grijelmo C, et al. Proinvasive activity of BMP-7 through SMAD4/src-independent and ERK/Rac/JNK-dependent signaling pathways in colon cancer cells. Cell Signal. 2007;19:1722–32.

    Article  PubMed  CAS  Google Scholar 

  12. Deng H, et al. Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells. Exp Cell Res. 2007;313:1033–44.

    Article  PubMed  CAS  Google Scholar 

  13. Zhao H, Ayrault O, Zindy F, Kim JH, Roussel MF. Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins suppresses medulloblastoma development. Genes Dev. 2008;22:722–7.

    Article  PubMed  CAS  Google Scholar 

  14. Langenfeld EM, et al. The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells. Carcinogenesis. 2003;24:1445–54.

    Article  PubMed  CAS  Google Scholar 

  15. Langenfeld EM, Kong Y, Langenfeld J. Bone morphogenetic protein 2 stimulation of tumor growth involves the activation of Smad-1/5. Oncogene. 2006;25:685–92.

    Article  PubMed  CAS  Google Scholar 

  16. Park Y. Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression. Med Oncol. 2009;27:1192–9.

    Article  PubMed  Google Scholar 

  17. Raida M, et al. Expression of bone morphogenetic protein 2 in breast cancer cells inhibits hypoxic cell death. Int J Oncol. 2005;26:1465–70.

    PubMed  CAS  Google Scholar 

  18. Shepherd TG, Theriault BL, Nachtigal MW. Autocrine BMP4 signalling regulates ID3 proto-oncogene expression in human ovarian cancer cells. Gene. 2008;414:95–105.

    Article  PubMed  CAS  Google Scholar 

  19. Jaffee EM, Hruban RH, Canto M, Kern SE. Focus on pancreas cancer. Cancer Cell. 2002;2:25–8.

    Article  PubMed  CAS  Google Scholar 

  20. Tang SY. Effect of bone morphogenetic protein-2 on the expression of membrane Type 1-matrix metalloproteinase in human A549 lung carcinoma cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008;33:634–7.

    Google Scholar 

  21. Hou CH, Hsiao YC, Fong YC, Tang CH. Bone morphogenetic protein-2 enhances the motility of chondrosarcoma cells via activation of matrix metalloproteinase-13. Bone. 2009;44:233–42.

    Article  PubMed  CAS  Google Scholar 

  22. Kang MH, et al. Inhibition of PI3 kinase/Akt pathway is required for BMP2-induced EMT and invasion. Oncol Rep. 2009;22:525–34.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Divisions of Hematology-Oncology, Department of Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-Dong 5-ga, Seongbul-gu, Seoul, 136-705, South Korea

    Yoon Ji Choi, Seung Tae Kim, Kyong Hwa Park, Sang Cheul Oh, Jae Hong Seo, Sang Won Shin, Jun Suk Kim & Yeul Hong Kim

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  1. Yoon Ji Choi
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  2. Seung Tae Kim
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  3. Kyong Hwa Park
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  7. Jun Suk Kim
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Correspondence to Yeul Hong Kim.

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Choi, Y.J., Kim, S.T., Park, K.H. et al. The serum bone morphogenetic protein-2 level in non-small-cell lung cancer patients. Med Oncol 29, 582–588 (2012). https://doi.org/10.1007/s12032-011-9852-9

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  • DOI: https://doi.org/10.1007/s12032-011-9852-9

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