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Article

Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis

Corrigendum in: /10.3892/ijo.2025.5757
  • Authors:
    • Weiwei Shen
    • Hailin Pang
    • Bo Xin
    • Lian Duan
    • Lili Liu
    • Helong Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
  • Pages: 1354-1362
    |
    Published online on: July 4, 2018
       https://doi.org/10.3892/ijo.2018.4469
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Abstract

Small-cell lung cancer (SCLC) is typically fatal if untreated. It is characterized by early and widespread metastases, and has the ability to rapidly develop resistance to chemotherapy. Bone morphogenetic protein 7 (BMP7), a member of the BMP family of signaling molecules, has been implicated in various types of cancer, particularly prostate cancer and breast cancer. However, there is little knowledge of the function of BMP7 in SCLC. The aim of the present study was to investigate the biological function of recombinant human (rh)BMP7 on SCLC cells and the underlying molecular basis for this regulatory mechanism. The effect of rhBMP7 on SCLC cell lines and associated signaling pathways was investigated. Results suggested that rhBMP7 significantly inhibited the proliferation, motility and invasion of SBC-3 and SBC-5 cells. However, rhBMP7 exhibited no effect on the apoptosis of SBC-5 cells, but promoted apoptosis of SBC-3 cells. Furthermore, cell cycle analysis revealed that rhBMP7 was able to increase the proportion of cells in G1 phase and decrease the S phase proportion. Total and membrane BMP receptor (BMPR)IA and BMPRIB were highly expressed in SBC-5 cells, whereas cytoplasmic BMPRIA and BMPRIB expression was higher in SBC-3 cells. However, activin A receptor type I expression was higher in SBC-3 cells in total and cytoplasmic proteins. Furthermore, following stimulation with rhBMP7, Smad2, Smad4 and p21 were downregulated. We hypothesized that rhBMP7 inhibited the progressiveness of SCLC cells by inducing G1 phase arrest and inhibiting S phase entry. The results of the present study indicated that BMP7 serves a key function in regulating the progression of SCLC.
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1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Graff JM: Embryonic patterning: To BMP or not to BMP, that is the question. Cell. 89:171–174. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Wozney JM and Rosen V: Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop Relat Res. 346:26–37. 1998. View Article : Google Scholar

4 

Urist MR: Bone: Formation by autoinduction. Science. 150:893–899. 1965. View Article : Google Scholar : PubMed/NCBI

5 

Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM and Wang EA: Novel regulators of bone formation: Molecular clones and activities. Science. 242:1528–1534. 1988. View Article : Google Scholar : PubMed/NCBI

6 

Boon MR, van der Horst G, van der Pluijm G, Tamsma JT, Smit JW and Rensen PC: Bone morphogenetic protein 7: A broad-spectrum growth factor with multiple target therapeutic potency. Cytokine Growth Factor Rev. 22:221–229. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, Ten Dijke P, Cleton-Jansen AM, Driouch K, et al: Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res. 67:8742–8751. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Buijs JT, Rentsch CA, van der Horst G, van Overveld PG, Wetterwald A, Schwaninger R, Henriquez NV, Ten Dijke P, Borovecki F, Markwalder R, et al: BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol. 171:1047–1057. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Botchkarev VA: Bone morphogenetic proteins and their antagonists in skin and hair follicle biology. J Invest Dermatol. 120:36–47. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Miyazono K, Maeda S and Imamura T: BMP receptor signaling: Transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16:251–263. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Kawabata M, Imamura T and Miyazono K: Signal transduction by bone morphogenetic proteins. Cytokine Growth Factor Rev. 9:49–61. 1998. View Article : Google Scholar : PubMed/NCBI

12 

Massagué J, Seoane J and Wotton D: Smad transcription factors. Genes Dev. 19:2783–2810. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

14 

ten Dijke P, Korchynskyi O, Valdimarsdottir G and Goumans MJ: Controlling cell fate by bone morphogenetic protein receptors. Mol Cell Endocrinol. 211:105–113. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Onichtchouk D, Chen YG, Dosch R, Gawantka V, Delius H, Massagué J and Niehrs C: Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature. 401:480–485. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Izpisua Belmonte JC and Choe S: Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 420:636–642. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Hsu DR, Economides AN, Wang X, Eimon PM and Harland RM: The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell. 1:673–683. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

19 

Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH and Park JH: Bone morphogenetic protein 7 induces mesenchymal-to-epithelial transition in melanoma cells, leading to inhibition of metastasis. Cancer Sci. 100:2218–2225. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Hsu MY, Rovinsky SA, Lai CY, Qasem S, Liu X, How J, Engelhardt JF and Murphy GF: Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation. Lab Invest. 88:842–855. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Klose A, Waerzeggers Y, Monfared P, Vukicevic S, Kaijzel EL, Winkeler A, Wickenhauser C, Löwik CW and Jacobs AH: Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas. Neoplasia. 13:276–285. 2011. View Article : Google Scholar : PubMed/NCBI

22 

González-Gómez P, Crecente-Campo J, Zahonero C, de la Fuente M, Hernández-Laín A, Mira H, Sánchez-Gómez P and Garcia-Fuentes M: Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma. Oncotarget. 6:10950–10963. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Sakai H, Furihata M, Matsuda C, Takahashi M, Miyazaki H, Konakahara T, Imamura T and Okada T: Augmented autocrine bone morphogenic protein (BMP) 7 signaling increases the metastatic potential of mouse breast cancer cells. Clin Exp Metastasis. 29:327–338. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Hu M, Cui F, Liu F, Wang J, Wei X and Li Y: BMP signaling pathways affect differently migration and invasion of esophageal squamous cancer cells. Int J Oncol. 50:193–202. 2017. View Article : Google Scholar

25 

Zhang T, Fu J, Li Y, Wang Y, Zhang L and Liu Y: Bone morphogenetic protein 7 is associated with the nodal invasion of colon cancer. Oncol Lett. 11:1707–1712. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Tu WH, Thomas TZ, Masumori N, Bhowmick NA, Gorska AE, Shyr Y, Kasper S, Case T, Roberts RL, Shappell SB, et al: The loss of TGF-beta signaling promotes prostate cancer metastasis. Neoplasia. 5:267–277. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Yang S, Zhong C, Frenkel B, Reddi AH and Roy-Burman P: Diverse biological effect and Smad signaling of bone morphogenetic protein 7 in prostate tumor cells. Cancer Res. 65:5769–5777. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Yang S, Lim M, Pham LK, Kendall SE, Reddi AH, Altieri DC and Roy-Burman P: Bone morphogenetic protein 7 protects prostate cancer cells from stress-induced apoptosis via both Smad and c-Jun NH2-terminal kinase pathways. Cancer Res. 66:4285–4290. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Bokobza SM, Ye L, Kynaston HE, Mansel RE and Jiang WG: Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells. Cancer Genomics Proteomics. 6:101–108. 2009.PubMed/NCBI

30 

Ye L, Lewis-Russell JM, Kynaston H and Jiang WG: Endogenous bone morphogenetic protein-7 controls the motility of prostate cancer cells through regulation of bone morphogenetic protein antagonists. J Urol. 178:1086–1091. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Ying X, Sun Y and He P: MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells. Oncotarget. 8:18348–18358. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Yin Y, Yang Y, Yang L, Yang Y, Li C, Liu X and Qu Y: Overexpression of Gremlin promotes non-small cell lung cancer progression. Tumour Biol. 37:2597–2602. 2016. View Article : Google Scholar

33 

Li X, Chen T, Shi Q, Li J, Cai S, Zhou P, Zhong Y and Yao L: Angiopoietin-like 4 enhances metastasis and inhibits apoptosis via inducing bone morphogenetic protein 7 in colorectal cancer cells. Biochem Biophys Res Commun. 467:128–134. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Megumi K, Ishigami S, Uchikado Y, Kita Y, Okumura H, Matsumoto M, Uenosono Y, Arigami T, Kijima Y, Kitazono M, et al: Clinicopathological significance of BMP7 expression in esophageal squamous cell carcinoma. Ann Surg Oncol. 19:2066–2071. 2012. View Article : Google Scholar :

35 

Aoki M, Ishigami S, Uenosono Y, Arigami T, Uchikado Y, Kita Y, Kurahara H, Matsumoto M, Ueno S and Natsugoe S: Expression of BMP-7 in human gastric cancer and its clinical significance. Br J Cancer. 104:714–718. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Xu G, Tang S, Yang J, Chen K, Kang J, Zhao G, Feng F, Yang X, Zhao L, Lu Q, et al: BMP7 expression in esophageal squamous cell carcinoma and its potential role in modulating metastasis. Dig Dis Sci. 58:1871–1879. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Kwak C, Park YH, Kim IY, Moon KC and Ku JH: Expression of bone morphogenetic proteins, the subfamily of the transforming growth factor-beta superfamily, in renal cell carcinoma. J Urol. 178:1062–1067. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shen W, Pang H, Xin B, Duan L, Liu L and Zhang H: Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757. Int J Oncol 53: 1354-1362, 2018.
APA
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., & Zhang, H. (2018). Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757. International Journal of Oncology, 53, 1354-1362. https://doi.org/10.3892/ijo.2018.4469
MLA
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., Zhang, H."Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757". International Journal of Oncology 53.3 (2018): 1354-1362.
Chicago
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., Zhang, H."Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757". International Journal of Oncology 53, no. 3 (2018): 1354-1362. https://doi.org/10.3892/ijo.2018.4469
Copy and paste a formatted citation
x
Spandidos Publications style
Shen W, Pang H, Xin B, Duan L, Liu L and Zhang H: Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757. Int J Oncol 53: 1354-1362, 2018.
APA
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., & Zhang, H. (2018). Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757. International Journal of Oncology, 53, 1354-1362. https://doi.org/10.3892/ijo.2018.4469
MLA
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., Zhang, H."Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757". International Journal of Oncology 53.3 (2018): 1354-1362.
Chicago
Shen, W., Pang, H., Xin, B., Duan, L., Liu, L., Zhang, H."Biological effects of BMP7 on small-cell lung cancer cells and its bone metastasis Corrigendum in /10.3892/ijo.2025.5757". International Journal of Oncology 53, no. 3 (2018): 1354-1362. https://doi.org/10.3892/ijo.2018.4469
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