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Article

GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway

  • Authors:
    • Guangfu Chen
    • Min Wang
    • Xiang Liu
  • View Affiliations / Copyright

    Affiliations: Department of Spine Surgery, The Affiliated Foshan Chancheng District Center Hospital of Guangdong Medical University, Foshan, Guangdong 528031, P.R. China
  • Pages: 4262-4270
    |
    Published online on: September 10, 2019
       https://doi.org/10.3892/mmr.2019.10664
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Abstract

Growth and differentiation factor 15 (GDF15), a novel divergent member of the transforming growth factor‑β (TGF‑β) superfamily, was previously reported to be overexpressed in various types of cancers and was shown to be involved in tumor metastasis; however, the role of GDF15 in the development and malignant progression of osteosarcoma remains unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction, western blot and ELISA analyses were performed to detect mRNA and protein expression, including that of GDF15, SMAD2 and SMAD3. Wound‑healing and cell invasion assays were conducted to determine the migratory and invasive abilities of osteosarcoma cells. A luciferase assay was performed to evaluate the transcriptional activity of a TGF‑β/SMAD‑responsive luciferase reporter. The Kaplan‑Meier method was used to generate survival curves, with a log‑rank test use to evaluate differences in survival. The results revealed that GDF15 expression was upregulated in metastatic osteosarcoma tissues compared with non‑metastatic osteosarcoma tissues. Patients with osteosarcoma that possessed high serum GDF15 levels exhibited significantly decreased overall survival (OS) and pulmonary metastasis‑free survival (PMFS) time compared with patients with low GDF15 expression. Furthermore, high serum GDF15 was an independent prognostic parameter for poor OS and short PMFS. Additionally, it was observed that the knockdown of GDF15 attenuated the migration and invasion of osteosarcoma cells. Silencing GDF15 markedly suppressed the TGF‑β signaling pathway. In conclusion, GDF15 may promote osteosarcoma cell metastasis by regulating the TGF‑β signaling pathway, and serum GDF15 levels may be a potential prognostic and pulmonary metastasis‑predictive biomarker in osteosarcoma.
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1 

Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: Data from the surveillance, epidemiology, and end results program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Marko TA, Diessner BJ and Spector LG: Prevalence of metastasis at diagnosis of osteosarcoma: An international comparison. Pediatr Blood Cancer. 63:1006–1011. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Duchman KR, Gao Y and Miller BJ: Prognostic factors for survival in patients with high-grade osteosarcoma using the Surveillance, Epidemiology, and End Results (SEER) Program database. Cancer Epidemiol. 39:593–599. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Kempf-Bielack B, Bielack SS, Jürgens H, Branscheid D, Berdel WE, Exner GU, Göbel U, Helmke K, Jundt G, Kabisch H, et al: Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 23:559–568. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Wu PK, Chen WM, Chen CF, Lee OK, Haung CK and Chen TH: Primary osteogenic sarcoma with pulmonary metastasis: Clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol. 39:514–522. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Goorin AM, Schwartzentruber DJ, Devidas M, Gebhardt MC, Ayala AG, Harris MB, Helman LJ, Grier HE and Link MP: Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric oncology group study POG-8651. J Clin Oncol. 21:1574–1580. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, Applewhite A, Vlamis V and Rosen G: Chemotherapy for nonmetastatic osteogenic sarcoma: The Memorial Sloan-Kettering experience. J Clin Oncol. 10:5–15. 1992. View Article : Google Scholar : PubMed/NCBI

8 

Chou AJ, Kleinerman ES, Krailo MD, Chen Z, Betcher DL, Healey JH, Conrad EU III, Nieder ML, Weiner MA, Wells RJ, et al: Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: A report from the Children's Oncology Group. Cancer. 115:5339–5348. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Bauskin AR, Brown DA, Kuffner T, Johnen H, Luo XW, Hunter M and Breit SN: Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 66:4983–4986. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Brown DA, Breit SN, Buring J, Fairlie WD, Bauskin AR, Liu T and Ridker PM: Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: A nested case-control study. Lancet. 359:2159–2163. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Brown DA, Ward RL, Buckhaults P, Liu T, Romans KE, Hawkins NJ, Bauskin AR, Kinzler KW, Vogelstein B and Breit SN: MIC-1 serum level and genotype: Associations with progress and prognosis of colorectal carcinoma. Clin Cancer Res. 9:2642–2650. 2003.PubMed/NCBI

12 

Tamary H, Shalev H, Perez-Avraham G, Zoldan M, Levi I, Swinkels DW, Tanno T and Miller JL: Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood. 112:5241–5244. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Staff AC, Trovik J, Eriksson AG, Wik E, Wollert KC, Kempf T and Salvesen HB: Elevated plasma growth differentiation factor-15 correlates with lymph node metastases and poor survival in endometrial cancer. Clin Cancer Res. 17:4825–4833. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Blanco-Calvo M, Tarrío N, Reboredo M, Haz-Conde M, García J, Quindós M, Figueroa A, Antón-Aparicio L, Calvo L and Valladares-Ayerbes M: Circulating levels of GDF15, MMP7 and miR-200c as a poor prognostic signature in gastric cancer. Future Oncol. 10:1187–1202. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Winand FJ, Boegemann M, Gallitz I, Hertle L, Semjonow A, Eveslage M, Van Aken HK, Herrmann E and Steinbicker AU: GDF15 and Hepcidin as prognostic factors in patients with prostate cancer. J Mol Biomark Diagn. 5:1992014.

16 

Enneking WF, Spanier SS and Goodman MA: A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 106–120. 1980.PubMed/NCBI

17 

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 : PubMed/NCBI

18 

Wang X, Ling MT, Guan XY, Tsao SW, Cheung HW, Lee DT and Wong YC: Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene. 23:474–482. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Kong KL, Kwong DL, Fu L, Chan TH, Chen L, Liu H, Li Y, Zhu YH, Bi J, Qin YR, et al: Characterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinoma. Cancer Res. 70:8832–8841. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Li Q, Ye L, Guo W, Wang M, Huang S and Peng X: PHF21B overexpression promotes cancer stem cell-like traits in prostate cancer cells by activating the Wnt/β-catenin signaling pathway. J Exp Clin Cancer Res. 36:852017. View Article : Google Scholar : PubMed/NCBI

21 

Endo-Munoz L, Cumming A, Rickwood D, Wilson D, Cueva C, Ng C, Strutton G, Cassady AI, Evdokiou A, Sommerville S, et al: Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases. Cancer Res. 70:7063–7072. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Böttner M, Suter-Crazzolara C, Schober A and Unsicker K: Expression of a novel member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues. Cell Tissue Res. 297:103–110. 1999. View Article : Google Scholar : PubMed/NCBI

23 

Sung JY, Park SY, Kim JH, Kang HG, Yoon JH, Na YS, Kim YN and Park BK: Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-β signaling in U2OS cells. Cell Death Dis. 5:e12242014. View Article : Google Scholar : PubMed/NCBI

24 

Kager L, Zoubek A, Pötschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, Kotz R, Salzer-Kuntschik M, Winkelmann W, et al: Primary metastatic osteosarcoma: Presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 21:2011–2018. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Geller DS and Gorlick R: Osteosarcoma: A review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 8:705–718. 2010.PubMed/NCBI

26 

Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, Sokoll LJ, Chan DW, Yeo CJ, Hruban RH, et al: Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res. 10:2386–2392. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Suesskind D, Schatz A, Schnichels S, Coupland SE, Lake SL, Wissinger B, Bartz-Schmidt KU and Henke-Fahle S: GDF-15: A novel serum marker for metastases in uveal melanoma patients. Graefes Arch Clin Exp Ophthalmol. 250:887–895. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Li PX, Wong J, Ayed A, Ngo D, Brade AM, Arrowsmith C, Austin RC and Klamut HJ: Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J Biol Chem. 275:20127–20135. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Baek SJ, Kim KS, Nixon JB, Wilson LC and Eling TE: Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol. 59:901–908. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Albertoni M, Shaw PH, Nozaki M, Godard S, Tenan M, Hamou MF, Fairlie DW, Breit SN, Paralkar VM, de Tribolet N, et al: Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1. Oncogene. 21:4212–4219. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Lee DH, Yang Y, Lee SJ, Kim KY, Koo TH, Shin SM, Song KS, Lee YH, Kim YJ, Lee JJ, et al: Macrophage inhibitory cytokine-1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system. Cancer Res. 63:4648–4655. 2003.PubMed/NCBI

32 

Liu T, Bauskin AR, Zaunders J, Brown DA, Pankhurst S, Russell PJ and Breit SN: Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res. 63:5034–5040. 2003.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen G, Wang M and Liu X: GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway. Mol Med Rep 20: 4262-4270, 2019.
APA
Chen, G., Wang, M., & Liu, X. (2019). GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway. Molecular Medicine Reports, 20, 4262-4270. https://doi.org/10.3892/mmr.2019.10664
MLA
Chen, G., Wang, M., Liu, X."GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 20.5 (2019): 4262-4270.
Chicago
Chen, G., Wang, M., Liu, X."GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 20, no. 5 (2019): 4262-4270. https://doi.org/10.3892/mmr.2019.10664
Copy and paste a formatted citation
x
Spandidos Publications style
Chen G, Wang M and Liu X: GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway. Mol Med Rep 20: 4262-4270, 2019.
APA
Chen, G., Wang, M., & Liu, X. (2019). GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway. Molecular Medicine Reports, 20, 4262-4270. https://doi.org/10.3892/mmr.2019.10664
MLA
Chen, G., Wang, M., Liu, X."GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 20.5 (2019): 4262-4270.
Chicago
Chen, G., Wang, M., Liu, X."GDF15 promotes osteosarcoma cell migration and invasion by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 20, no. 5 (2019): 4262-4270. https://doi.org/10.3892/mmr.2019.10664
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