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Neuropilin-1 is overexpressed in osteosarcoma and contributes to tumor progression and poor prognosis

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Abstract

Aim

Neuropilin (NRP)-1, a co-receptor for vascular endothelial growth factor (VEGF), plays an important role in angiogenesis and malignant progression of many cancers. However, the involvement of NRP-1 in osteosarcoma is not completely understood. The aim of this study was to investigate the expression pattern and clinical significance of NRP-1 in human osteosarcoma.

Methods

NRP-1 mRNA and protein expression levels were detected by RT-PCR and Western blot assays, respectively, using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the association of NRP-1 expression with clinicopathological factors or survival of osteosarcoma patients was further evaluated.

Results

RT-PCR and Western blot assays revealed that NRP-1 expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues at both mRNA and protein levels (both P < 0.001). In addition, high NRP-1 expression more frequently occurred in osteosarcoma tissues with advanced clinical stage (P = 0.006), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.006). Moreover, osteosarcoma patients with high NRP-1 expression had significantly shorter overall survival and disease-free survival (both P < 0.001) when compared with patients with the low expression of NRP-1. On Cox multivariate analysis, NRP-1 overexpression was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both P = 0.001).

Conclusion

This is the first study to reveal that NRP-1 overexpression may be related to the prediction of metastasis potency, response to chemotherapy and poor prognosis for osteosarcoma patients, suggesting that NRP-1 may serve as a prognostic marker for the optimization of clinical treatments.

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References

  1. Gill J, Ahluwalia MK, Geller D, Gorlick R. New targets and approaches in osteosarcoma. Pharmacol Ther. 2013;137:89–99.

    Article  CAS  PubMed  Google Scholar 

  2. Lee JA, Kim MS, Kim DH, Lim JS, Yoo JY, Koh JS, et al. Relative tumor burden predicts metastasis-free survival in pediatric osteosarcoma. Pediatr Blood Cancer. 2008;50:195–200.

    Article  PubMed  Google Scholar 

  3. Jaffe N. Adjuvant chemotherapy in osteosarcoma: An odyssey of rejection and vindication. In: Jaffe N, Bielack SS, Bruland OS, editors. Pediatric and adolescent osteosarcoma, cancer treatment and research. New York: Springer; 2009. p. 152.

    Google Scholar 

  4. Bakhshi S, Radhakrishnan V. Prognostic markers in osteosarcoma. Expert Rev Anticancer Ther. 2010;10:271–87.

    Article  PubMed  Google Scholar 

  5. Magnan H, Chou AJ, Chou JF, Yeung HW, Healey JH, Meyers PA. Noninvasive imaging with thallium-201 scintigraphy may not correlate with survival in patients with osteosarcoma. Cancer. 2010;116:4147–51.

    Article  PubMed  Google Scholar 

  6. He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell. 1997;90:739–51.

    Article  CAS  PubMed  Google Scholar 

  7. Staton CA, Kumar I, Reed MW, Brown NJ. Neuropilins in physiological and pathological angiogenesis. J Pathol. 2007;212:237–48.

    Article  CAS  PubMed  Google Scholar 

  8. Wild JR, Staton CA, Chapple K, Corfe BM. Neuropilins: expression and roles in the epithelium. Int J Exp Pathol. 2012;93:81–103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Lanahan A, Zhang X, Fantin A, Zhuang Z, Rivera-Molina F, Speichinger K, et al. The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. Dev Cell. 2013;25:156–68.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Song X, Zhang W, Zhang Y, Zhang H, Fu Z, Ye J, et al. Expression of semaphorin 3A and neuropilin 1 with clinicopathological features and survival in human tongue cancer. Med Oral Patol Oral Cir Bucal. 2012;17:e962–8.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Talagas M, Uguen A, Garlantezec R, Fournier G, Doucet L, Gobin E, et al. VEGFR1 and NRP1 endothelial expressions predict distant relapse after radical prostatectomy in clinically localized prostate cancer. Anticancer Res. 2013;33:2065–75.

    CAS  PubMed  Google Scholar 

  12. Staton CA, Koay I, Wu JM, Hoh L, Reed MW, Brown NJ. Neuropilin-1 and neuropilin-2 expression in the adenoma-carcinoma sequence of colorectal cancer. Histopathology. 2013;62:908–15.

    Article  PubMed  Google Scholar 

  13. Bergé M, Allanic D, Bonnin P, de Montrion C, Richard J, Suc M, et al. Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling. J Hepatol. 2011;55:866–75.

    Article  PubMed  Google Scholar 

  14. Ambroszkiewicz J, Gajewska J, Klepacka T, Chelchowska M, Laskowska-Klita T, Wozniak W. Clinical utility of biochemical bone turnover markers in children and adolescents with osteosarcoma. Adv Med Sci. 2010;55:266–72.

    Article  CAS  PubMed  Google Scholar 

  15. Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 2002;20:776–90.

    Article  PubMed  Google Scholar 

  16. Lee YH, Tokunaga T, Oshika Y, Suto R, Yanagisawa K, Tomisawa M, et al. Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma. Eur J Cancer. 1999;35:1089–93.

    Article  CAS  PubMed  Google Scholar 

  17. Kaya M, Wada T, Nagoya S, Sasaki M, Matsumura T, Yamashita T. The level of vascular endothelial growth factor as a predictor of a poor prognosis in osteosarcoma. J Bone Joint Surg Br. 2009;91:784–8.

    Article  CAS  PubMed  Google Scholar 

  18. Jung ST, Moon ES, Seo HY, Kim JS, Kim GJ, Kim YK. Expression and significance of TGF-beta isoform and VEGF in osteosarcoma. Orthopedics. 2005;28:755–60.

    PubMed  Google Scholar 

  19. Handa A, Tokunaga T, Tsuchida T, Lee YH, Kijima H, Yamazaki H, et al. Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma. Int J Oncol. 2000;17:291–5.

    CAS  PubMed  Google Scholar 

  20. Yukata K, Matsui Y, Goto T, Kubo T, Yasui N. Differential expression of VEGF isoforms and VEGF receptors in cartilaginous tumors. Anticancer Res. 2005;25:955–7.

    CAS  PubMed  Google Scholar 

  21. Huvos AG. Osteosarcoma in adolescents and young adults: new developments and controversies. Commentary on pathology. Cancer Treat Res. 1993;62:375–7.

    Article  CAS  PubMed  Google Scholar 

  22. Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–30.

    Article  CAS  PubMed  Google Scholar 

  23. Tang J, Cai H, Lin L, Xie P, Zhong W, Tang M. Increased expression of CD24 is associated with tumor progression and prognosis in patients suffering osteosarcoma. Clin Transl Oncol. 2013;15:541–7.

    Article  CAS  PubMed  Google Scholar 

  24. Glinka Y, Mohammed N, Subramaniam V, Jothy S, Prud’homme GJ. Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation. Biochem Biophys Res Commun. 2012;425:775–80.

    Article  CAS  PubMed  Google Scholar 

  25. Cao Y, E G, Wang E, Pal K, Dutta SK, Bar-Sagi D, et al. VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression. Cancer Res. 2012;72:3912–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Jubb AM, Strickland LA, Liu SD, Mak J, Schmidt M, Koeppen H. Neuropilin-1 expression in cancer and development. J Pathol. 2012;226:50–60.

    Article  CAS  PubMed  Google Scholar 

  27. Glinka Y, Stoilova S, Mohammed N, Prud’homme GJ. Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer cells and enhances responses to both latent and active TGF-beta. Carcinogenesis. 2011;32:613–21.

    Article  CAS  PubMed  Google Scholar 

  28. Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, et al. Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res. 2007;13:4759–68.

    Article  CAS  PubMed  Google Scholar 

  29. Castro-Rivera E, Ran S, Brekken RA, Minna JD. Semaphorin 3B inhibits the phosphatidylinositol 3-kinase/Akt pathway through neuropilin-1 in lung and breast cancer cells. Cancer Res. 2008;68:8295–303.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Orthopaedics Department, Xuhui Central Hospital, No.966, Middle Huaihai Road, Shanghai, 200031, China

    H. Zhu, H. Cai & J. Tang

  2. Orthopaedics Department, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, 200233, China

    M. Tang

Authors
  1. H. Zhu
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  2. H. Cai
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  3. M. Tang
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  4. J. Tang
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Corresponding author

Correspondence to J. Tang.

Additional information

H. Zhu, H. Cai and M. Tang contributed equally to this article.

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Zhu, H., Cai, H., Tang, M. et al. Neuropilin-1 is overexpressed in osteosarcoma and contributes to tumor progression and poor prognosis. Clin Transl Oncol 16, 732–738 (2014). https://doi.org/10.1007/s12094-013-1141-y

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  • DOI: https://doi.org/10.1007/s12094-013-1141-y

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