Advertisement

Cancer and Metastasis Reviews

, Volume 37, Issue 4, pp 719–731 | Cite as

From genomics to metabolomics: emerging metastatic biomarkers in osteosarcoma

  • Dylan C. Dean
  • Shen Shen
  • Francis J. Hornicek
  • Zhenfeng DuanEmail author
Article

Abstract

Although the investigation into biomarkers specific for pulmonary metastasis within osteosarcoma (OS) has recently expanded, their usage within the clinic remains sparse. The current screening protocol after any OS diagnosis includes a chest CT scan; however, metastatic lung nodules frequently go undetected and remain the primary cause of death in OS. Recently, screening technologies such as liquid biopsy and next-generation sequencing have revealed a promising array of biomarkers with predictive and diagnostic value for the pulmonary metastasis associated with OS. These biomarkers draw from genomics, transcriptomics, epigenetics, and metabolomics. When assessed in concert, their utility is most promising as OS is a highly heterogeneous cancer. Accordingly, there has been an expansion of clinical trials not only aimed at further demonstrating the significance of these individual biomarkers but to also reveal which therapies resolve the pulmonary metastasis once detected. This review will focus on the recently discovered and novel metastatic biomarkers within OS, their molecular and cellular mechanisms, the expansion of humanized OS mouse models amenable to their testing, and the associated clinical trials aimed at managing the metastatic phase of OS.

Keywords

Osteosarcoma Metastasis Metabolomics ncRNA Clinical trial 

Notes

Funding

This work was supported, in part, by the Department of Orthopaedic Surgery at UCLA. Dr. Duan is supported, in part, through a Grant from Sarcoma Foundation of America (SFA), a Grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA151452-01.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kansara, M., Teng, M. W., Smyth, M. J., & Thomas, D. M. (2014). Translational biology of osteosarcoma. Nature Reviews. Cancer, 14(11), 722–735.  https://doi.org/10.1038/nrc3838.CrossRefGoogle Scholar
  2. 2.
    Lu, J., Song, G., Tang, Q., Zou, C., Han, F., Zhao, Z., Yong, B., Yin, J., Xu, H., Xie, X., Kang, T., Lam, Y. L., Yang, H., Shen, J., & Wang, J. (2015). IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-kappaB signaling. The Journal of Clinical Investigation, 125(5), 1839–1856.  https://doi.org/10.1172/JCI78437.CrossRefGoogle Scholar
  3. 3.
    Yu, W., Tang, L., Lin, F., Li, D., Wang, J., Yang, Y., et al. (2014). Stereotactic radiosurgery, a potential alternative treatment for pulmonary metastases from osteosarcoma. International Journal of Oncology, 44(4), 1091–1098.  https://doi.org/10.3892/ijo.2014.2295.CrossRefGoogle Scholar
  4. 4.
    Bacci, G., Briccoli, A., Rocca, M., Ferrari, S., Donati, D., Longhi, A., Bertoni, F., Bacchini, P., Giacomini, S., Forni, C., Manfrini, M., & Galletti, S. (2003). Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: Recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology, 14(7), 1126–1134.CrossRefGoogle Scholar
  5. 5.
    Geller, D. S., & Gorlick, R. (2010). Osteosarcoma: A review of diagnosis, management, and treatment strategies. Clinical Advances in Hematology & Oncology, 8(10), 705–718.Google Scholar
  6. 6.
    Isakoff, M. S., Bielack, S. S., Meltzer, P., & Gorlick, R. (2015). Osteosarcoma: Current treatment and a collaborative pathway to success. Journal of Clinical Oncology, 33(27), 3029–3035.  https://doi.org/10.1200/JCO.2014.59.4895.CrossRefGoogle Scholar
  7. 7.
    Briccoli, A., Rocca, M., Salone, M., Bacci, G., Ferrari, S., Balladelli, A., & Mercuri, M. (2005). Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer, 104(8), 1721–1725.  https://doi.org/10.1002/cncr.21369.CrossRefGoogle Scholar
  8. 8.
    Min, L., Choy, E., Tu, C., Hornicek, F., & Duan, Z. (2017). Application of metabolomics in sarcoma: From biomarkers to therapeutic targets. Critical Reviews in Oncology/Hematology, 116, 1–10.  https://doi.org/10.1016/j.critrevonc.2017.05.003.CrossRefGoogle Scholar
  9. 9.
    Perry, J. A., Kiezun, A., Tonzi, P., Van Allen, E. M., Carter, S. L., Baca, S. C., et al. (2014). Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proceedings of the National Academy of Sciences of the United States of America, 111(51), E5564–E5573.  https://doi.org/10.1073/pnas.1419260111.CrossRefGoogle Scholar
  10. 10.
    Allegretti, M., Casini, B., Mandoj, C., Benini, S., Alberti, L., Novello, M., Melucci, E., Conti, L., Covello, R., Pescarmona, E., Milano, G. M., Annovazzi, A., Anelli, V., Ferraresi, V., Biagini, R., & Giacomini, P. (2018). Precision diagnostics of Ewing’s sarcoma by liquid biopsy: Circulating EWS-FLI1 fusion transcripts. Ther Adv Med Oncol, 10, 1758835918774337.  https://doi.org/10.1177/1758835918774337.CrossRefGoogle Scholar
  11. 11.
    Bersani, F., Lingua, M. F., Morena, D., Foglizzo, V., Miretti, S., Lanzetti, L., Carra, G., Morotti, A., Ala, U., Provero, P., Chiarle, R., Singer, S., Ladanyi, M., Tuschl, T., Ponzetto, C., & Taulli, R. (2016). Deep sequencing reveals a novel miR-22 regulatory network with therapeutic potential in rhabdomyosarcoma. Cancer Research, 76(20), 6095–6106.  https://doi.org/10.1158/0008-5472.CAN-16-0709.CrossRefGoogle Scholar
  12. 12.
    Chen, K., Fallen, S., Abaan, H. O., Hayran, M., Gonzalez, C., Wodajo, F., MacDonald, T., Toretsky, J. A., & Üren, A. (2008). Wnt10b induces chemotaxis of osteosarcoma and correlates with reduced survival. Pediatric Blood & Cancer, 51(3), 349–355.  https://doi.org/10.1002/pbc.21595.CrossRefGoogle Scholar
  13. 13.
    Guo, M., Cai, C., Zhao, G., Qiu, X., Zhao, H., Ma, Q., Tian, L., Li, X., Hu, Y., Liao, B., Ma, B., & Fan, Q. (2014). Hypoxia promotes migration and induces CXCR4 expression via HIF-1alpha activation in human osteosarcoma. PLoS One, 9(3), e90518.  https://doi.org/10.1371/journal.pone.0090518.CrossRefGoogle Scholar
  14. 14.
    Cao, J., Wang, Y., Dong, R., Lin, G., Zhang, N., Wang, J., Lin, N., Gu, Y., Ding, L., Ying, M., He, Q., & Yang, B. (2015). Hypoxia-induced WSB1 promotes the metastatic potential of osteosarcoma cells. Cancer Research, 75(22), 4839–4851.  https://doi.org/10.1158/0008-5472.CAN-15-0711.CrossRefGoogle Scholar
  15. 15.
    Jones, K. B., Salah, Z., Del Mare, S., Galasso, M., Gaudio, E., Nuovo, G. J., et al. (2012). miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Research, 72(7), 1865–1877.  https://doi.org/10.1158/0008-5472.CAN-11-2663.CrossRefGoogle Scholar
  16. 16.
    Salah, Z., Arafeh, R., Maximov, V., Galasso, M., Khawaled, S., Abou-Sharieha, S., et al. (2015). miR-27a and miR-27a* contribute to metastatic properties of osteosarcoma cells. Oncotarget, 6(7), 4920–4935.  https://doi.org/10.18632/oncotarget.3025.CrossRefGoogle Scholar
  17. 17.
    Pan, W., Wang, H., Jianwei, R., & Ye, Z. (2014). MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. Cellular Physiology and Biochemistry, 33(2), 402–412.  https://doi.org/10.1159/000356679.CrossRefGoogle Scholar
  18. 18.
    Huang, G., Nishimoto, K., Zhou, Z., Hughes, D., & Kleinerman, E. S. (2012). miR-20a encoded by the miR-17-92 cluster increases the metastatic potential of osteosarcoma cells by regulating Fas expression. Cancer Research, 72(4), 908–916.  https://doi.org/10.1158/0008-5472.CAN-11-1460.CrossRefGoogle Scholar
  19. 19.
    Hua, Y., Qiu, Y., Zhao, A., Wang, X., Chen, T., Zhang, Z., Chi, Y., Li, Q., Sun, W., Li, G., Cai, Z., Zhou, Z., & Jia, W. (2011). Dynamic metabolic transformation in tumor invasion and metastasis in mice with LM-8 osteosarcoma cell transplantation. Journal of Proteome Research, 10(8), 3513–3521.  https://doi.org/10.1021/pr200147g.CrossRefGoogle Scholar
  20. 20.
    Ren, L., Hong, E. S., Mendoza, A., Issaq, S., Tran Hoang, C., Lizardo, M., et al. (2017). Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis. Oncotarget, 8(24), 38541–38553.  https://doi.org/10.18632/oncotarget.15872.CrossRefGoogle Scholar
  21. 21.
    Sottnik, J. L., Lori, J. C., Rose, B. J., & Thamm, D. H. (2011). Glycolysis inhibition by 2-deoxy-D-glucose reverts the metastatic phenotype in vitro and in vivo. Clinical & Experimental Metastasis, 28(8), 865–875.  https://doi.org/10.1007/s10585-011-9417-5.CrossRefGoogle Scholar
  22. 22.
    Singh, N., Das, P., Gupta, S., Sachdev, V., Srivasatava, S., Datta Gupta, S., Pandey, R. M., Sahni, P., Chauhan, S. S., & Saraya, A. (2014). Plasma cathepsin L: A prognostic marker for pancreatic cancer. World Journal of Gastroenterology, 20(46), 17532–17540.  https://doi.org/10.3748/wjg.v20.i46.17532.CrossRefGoogle Scholar
  23. 23.
    Macklin, R., Wang, H., Loo, D., Martin, S., Cumming, A., Cai, N., et al. (2016). Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones. Oncotarget, 7(28), 43570–43587.  https://doi.org/10.18632/oncotarget.9781.CrossRefGoogle Scholar
  24. 24.
    Wang, B., Su, Y., Yang, Q., Lv, D., Zhang, W., Tang, K., et al. (2015). Overexpression of long non-coding RNA HOTAIR promotes tumor growth and metastasis in human osteosarcoma. Mol Cells, 38(5), 432–440.  https://doi.org/10.14348/molcells.2015.2327.CrossRefGoogle Scholar
  25. 25.
    Ruan, W., Wang, P., Feng, S., Xue, Y., & Li, Y. (2016). Long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) promotes cell proliferation and migration by upregulating angiomotin gene expression in human osteosarcoma cells. Tumour Biology, 37(3), 4065–4073.  https://doi.org/10.1007/s13277-015-4256-7.CrossRefGoogle Scholar
  26. 26.
    Zhou, S., Yu, L., Xiong, M., & Dai, G. (2018). LncRNA SNHG12 promotes tumorigenesis and metastasis in osteosarcoma by upregulating Notch2 by sponging miR-195-5p. Biochemical and Biophysical Research Communications, 495(2), 1822–1832.  https://doi.org/10.1016/j.bbrc.2017.12.047.CrossRefGoogle Scholar
  27. 27.
    Sun, J., Wang, X., Fu, C., Wang, X., Zou, J., Hua, H., & Bi, Z. (2016). Long noncoding RNA FGFR3-AS1 promotes osteosarcoma growth through regulating its natural antisense transcript FGFR3. Molecular Biology Reports, 43(5), 427–436.  https://doi.org/10.1007/s11033-016-3975-1.CrossRefGoogle Scholar
  28. 28.
    Dong, Y., Liang, G., Yuan, B., Yang, C., Gao, R., & Zhou, X. (2015). MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biology, 36(3), 1477–1486.  https://doi.org/10.1007/s13277-014-2631-4.CrossRefGoogle Scholar
  29. 29.
    Jin, H., Jin, X., Zhang, H., & Wang, W. (2017). Circular RNA hsa-circ-0016347 promotes proliferation, invasion and metastasis of osteosarcoma cells. Oncotarget, 8(15), 25571–25581.  https://doi.org/10.18632/oncotarget.16104.Google Scholar
  30. 30.
    Liu, X., Zhong, Y., Li, J., & Shan, A. (2017). Circular RNA circ-NT5C2 acts as an oncogene in osteosarcoma proliferation and metastasis through targeting miR-448. Oncotarget, 8(70), 114829–114838.  https://doi.org/10.18632/oncotarget.22162.Google Scholar
  31. 31.
    Huang, L., Chen, M., Pan, J., & Yu, W. (2018). Circular RNA circNASP modulates the malignant behaviors in osteosarcoma via miR-1253/FOXF1 pathway. Biochemical and Biophysical Research Communications, 500(2), 511–517.  https://doi.org/10.1016/j.bbrc.2018.04.131.CrossRefGoogle Scholar
  32. 32.
    Xiao-Long, M., Kun-Peng, Z., & Chun-Lin, Z. (2018). Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma. Journal of Cancer, 9(10), 1856–1862.  https://doi.org/10.7150/jca.24619.CrossRefGoogle Scholar
  33. 33.
    Bao, Q., Gong, L., Wang, J., Wen, J., Shen, Y., & Zhang, W. (2018). Extracellular vesicle RNA sequencing reveals dramatic transcriptomic alterations between metastatic and primary osteosarcoma in a liquid biopsy approach. Annals of Surgical Oncology, 25, 2642–2651.  https://doi.org/10.1245/s10434-018-6642-z.CrossRefGoogle Scholar
  34. 34.
    Clevers, H., & Nusse, R. (2012). Wnt/beta-catenin signaling and disease. Cell, 149(6), 1192–1205.  https://doi.org/10.1016/j.cell.2012.05.012.CrossRefGoogle Scholar
  35. 35.
    Nusse, R., & Clevers, H. (2017). Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities. Cell, 169(6), 985–999.  https://doi.org/10.1016/j.cell.2017.05.016.CrossRefGoogle Scholar
  36. 36.
    Zhao, S., Kurenbekova, L., Gao, Y., Roos, A., Creighton, C. J., Rao, P., Hicks, J., Man, T. K., Lau, C., Brown, A. M. C., Jones, S. N., Lazar, A. J., Ingram, D., Lev, D., Donehower, L. A., & Yustein, J. T. (2015). NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma. Oncogene, 34(39), 5069–5079.  https://doi.org/10.1038/onc.2014.429.CrossRefGoogle Scholar
  37. 37.
    Zhao, S. J., Jiang, Y. Q., Xu, N. W., Li, Q., Zhang, Q., Wang, S. Y., Li, J., Wang, Y. H., Zhang, Y. L., Jiang, S. H., Wang, Y. J., Huang, Y. J., Zhang, X. X., Tian, G. A., Zhang, C. C., Lv, Y. Y., Dai, M., Liu, F., Zhang, R., Zhou, D., & Zhang, Z. G. (2018). SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/beta-catenin signaling through stabilization of the WNT-receptor complex. Oncogene, 37(8), 1049–1061.  https://doi.org/10.1038/onc.2017.403.CrossRefGoogle Scholar
  38. 38.
    Semenza, G. L. (2011). Oxygen sensing, homeostasis, and disease. The New England Journal of Medicine, 365(6), 537–547.  https://doi.org/10.1056/NEJMra1011165.CrossRefGoogle Scholar
  39. 39.
    Dewhirst, M. W., Ong, E. T., Rosner, G. L., Rehmus, S. W., Shan, S., Braun, R. D., Brizel, D. M., & Secomb, T. W. (1996). Arteriolar oxygenation in tumour and subcutaneous arterioles: Effects of inspired air oxygen content. The British Journal of Cancer. Supplement, 27, S241–S246.Google Scholar
  40. 40.
    Harada, R., Kawamoto, T., Ueha, T., Minoda, M., Toda, M., Onishi, Y., Fukase, N., Hara, H., Sakai, Y., Miwa, M., Kuroda, R., Kurosaka, M., & Akisue, T. (2013). Reoxygenation using a novel CO2 therapy decreases the metastatic potential of osteosarcoma cells. Experimental Cell Research, 319(13), 1988–1997.  https://doi.org/10.1016/j.yexcr.2013.05.019.CrossRefGoogle Scholar
  41. 41.
    Liapis, V., Labrinidis, A., Zinonos, I., Hay, S., Ponomarev, V., Panagopoulos, V., DeNichilo, M., Ingman, W., Atkins, G. J., Findlay, D. M., Zannettino, A. C. W., & Evdokiou, A. (2015). Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma. Cancer Letters, 357(1), 160–169.  https://doi.org/10.1016/j.canlet.2014.11.020.CrossRefGoogle Scholar
  42. 42.
    Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the National Academy of Sciences of the United States of America, 92(12), 5510–5514.CrossRefGoogle Scholar
  43. 43.
    Abdeen, A., Chou, A. J., Healey, J. H., Khanna, C., Osborne, T. S., Hewitt, S. M., Kim, M., Wang, D., Moody, K., & Gorlick, R. (2009). Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer, 115(22), 5243–5250.  https://doi.org/10.1002/cncr.24562.CrossRefGoogle Scholar
  44. 44.
    Hartmann, T. N., Burger, J. A., Glodek, A., Fujii, N., & Burger, M. (2005). CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells. Oncogene, 24(27), 4462–4471.  https://doi.org/10.1038/sj.onc.1208621.CrossRefGoogle Scholar
  45. 45.
    Archange, C., Nowak, J., Garcia, S., Moutardier, V., Calvo, E. L., Dagorn, J. C., & Iovanna, J. L. (2008). The WSB1 gene is involved in pancreatic cancer progression. PLoS One, 3(6), e2475.  https://doi.org/10.1371/journal.pone.0002475.CrossRefGoogle Scholar
  46. 46.
    Tong, Y., Li, Q. G., Xing, T. Y., Zhang, M., Zhang, J. J., & Xia, Q. (2013). HIF1 regulates WSB-1 expression to promote hypoxia-induced chemoresistance in hepatocellular carcinoma cells. FEBS Letters, 587(16), 2530–2535.  https://doi.org/10.1016/j.febslet.2013.06.017.CrossRefGoogle Scholar
  47. 47.
    Scott, M. C., Temiz, N. A., Sarver, A. E., LaRue, R. S., Rathe, S. K., Varshney, J., Wolf, N. K., Moriarity, B. S., O'Brien, T. D., Spector, L. G., Largaespada, D. A., Modiano, J. F., Subramanian, S., & Sarver, A. L. (2018). Comparative transcriptome analysis quantifies immune cell transcript levels, metastatic progression, and survival in osteosarcoma. Cancer Research, 78(2), 326–337.  https://doi.org/10.1158/0008-5472.CAN-17-0576.CrossRefGoogle Scholar
  48. 48.
    Nicoloso, M. S., Spizzo, R., Shimizu, M., Rossi, S., & Calin, G. A. (2009). MicroRNAs—the micro steering wheel of tumour metastases. Nature Reviews. Cancer, 9(4), 293–302.  https://doi.org/10.1038/nrc2619.CrossRefGoogle Scholar
  49. 49.
    Rodriguez Calleja, L., Jacques, C., Lamoureux, F., Baud'huin, M., Tellez Gabriel, M., Quillard, T., Sahay, D., Perrot, P., Amiaud, J., Charrier, C., Brion, R., Lecanda, F., Verrecchia, F., Heymann, D., Ellisen, L. W., & Ory, B. (2016). DeltaNp63alpha silences a miRNA program to aberrantly initiate a wound-healing program that promotes TGFbeta-induced metastasis. Cancer Research, 76(11), 3236–3251.  https://doi.org/10.1158/0008-5472.CAN-15-2317.CrossRefGoogle Scholar
  50. 50.
    Frampton, A. E., Castellano, L., Colombo, T., Giovannetti, E., Krell, J., Jacob, J., et al. (2015). Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression. Lancet, 385(Suppl 1), S37.  https://doi.org/10.1016/S0140-6736(15)60352-X.CrossRefGoogle Scholar
  51. 51.
    Liu, T., Tang, H., Lang, Y., Liu, M., & Li, X. (2009). MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Letters, 273(2), 233–242.  https://doi.org/10.1016/j.canlet.2008.08.003.CrossRefGoogle Scholar
  52. 52.
    Mertens-Talcott, S. U., Chintharlapalli, S., Li, X., & Safe, S. (2007). The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Research, 67(22), 11001–11011.  https://doi.org/10.1158/0008-5472.CAN-07-2416.CrossRefGoogle Scholar
  53. 53.
    Koshkina, N. V., Khanna, C., Mendoza, A., Guan, H., DeLauter, L., & Kleinerman, E. S. (2007). Fas-negative osteosarcoma tumor cells are selected during metastasis to the lungs: The role of the Fas pathway in the metastatic process of osteosarcoma. Molecular Cancer Research, 5(10), 991–999.  https://doi.org/10.1158/1541-7786.MCR-07-0007.CrossRefGoogle Scholar
  54. 54.
    Gordon, N., Koshkina, N. V., Jia, S. F., Khanna, C., Mendoza, A., Worth, L. L., & Kleinerman, E. S. (2007). Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine. Clinical Cancer Research, 13(15 Pt 1), 4503–4510.  https://doi.org/10.1158/1078-0432.CCR-07-0313.CrossRefGoogle Scholar
  55. 55.
    Huang, G., Nishimoto, K., Yang, Y., & Kleinerman, E. S. (2014). Participation of the Fas/FasL signaling pathway and the lung microenvironment in the development of osteosarcoma lung metastases. Advances in Experimental Medicine and Biology, 804, 203–217.  https://doi.org/10.1007/978-3-319-04843-7_11.CrossRefGoogle Scholar
  56. 56.
    Yang, Z., Li, X., Yang, Y., He, Z., Qu, X., & Zhang, Y. (2016). Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. Cell Death & Disease, 7(9), e2389.  https://doi.org/10.1038/cddis.2016.272.CrossRefGoogle Scholar
  57. 57.
    Tan, S. K., Pastori, C., Penas, C., Komotar, R. J., Ivan, M. E., Wahlestedt, C., & Ayad, N. G. (2018). Serum long noncoding RNA HOTAIR as a novel diagnostic and prognostic biomarker in glioblastoma multiforme. Molecular Cancer, 17(1), 74.  https://doi.org/10.1186/s12943-018-0822-0.CrossRefGoogle Scholar
  58. 58.
    Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E. (2013). Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19(2), 141–157.  https://doi.org/10.1261/rna.035667.112.CrossRefGoogle Scholar
  59. 59.
    Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., & Kjems, J. (2013). Natural RNA circles function as efficient microRNA sponges. Nature, 495(7441), 384–388.  https://doi.org/10.1038/nature11993.CrossRefGoogle Scholar
  60. 60.
    Zhou, X., Gao, Q., Wang, J., Zhang, X., Liu, K., & Duan, Z. (2014). Linc-RNA-RoR acts as a "sponge" against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecologic Oncology, 133(2), 333–339.  https://doi.org/10.1016/j.ygyno.2014.02.033.CrossRefGoogle Scholar
  61. 61.
    Wu, X., Yan, L., Liu, Y., Xian, W., Wang, L., & Ding, X. (2017). MicroRNA-448 suppresses osteosarcoma cell proliferation and invasion through targeting EPHA7. PLoS One, 12(6), e0175553.  https://doi.org/10.1371/journal.pone.0175553.CrossRefGoogle Scholar
  62. 62.
    Li, Y., Zheng, F., Xiao, X., Xie, F., Tao, D., Huang, C., et al. (2017). CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep, 18(9), 1646–1659.  https://doi.org/10.15252/embr.201643581.CrossRefGoogle Scholar
  63. 63.
    Zheng, Q., Bao, C., Guo, W., Li, S., Chen, J., Chen, B., Luo, Y., Lyu, D., Li, Y., Shi, G., Liang, L., Gu, J., He, X., & Huang, S. (2016). Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nature Communications, 7, 11215.  https://doi.org/10.1038/ncomms11215.CrossRefGoogle Scholar
  64. 64.
    Wojakowska, A., Chekan, M., Widlak, P., & Pietrowska, M. (2015). Application of metabolomics in thyroid cancer research. International Journal of Endocrinology, 2015, 258763–258713.  https://doi.org/10.1155/2015/258763.CrossRefGoogle Scholar
  65. 65.
    Holmes, E., Wilson, I. D., & Nicholson, J. K. (2008). Metabolic phenotyping in health and disease. Cell, 134(5), 714–717.  https://doi.org/10.1016/j.cell.2008.08.026.CrossRefGoogle Scholar
  66. 66.
    DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008). The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism, 7(1), 11–20.  https://doi.org/10.1016/j.cmet.2007.10.002.CrossRefGoogle Scholar
  67. 67.
    Kort, W. J., Hulsmann, W. C., & Stehman, T. E. (1989). Modulation of metastatic ability by inhibition of cholesterol synthesis. Clinical & Experimental Metastasis, 7(5), 517–523.CrossRefGoogle Scholar
  68. 68.
    Chen, E. I., Hewel, J., Krueger, J. S., Tiraby, C., Weber, M. R., Kralli, A., Becker, K., Yates, J. R., & Felding-Habermann, B. (2007). Adaptation of energy metabolism in breast cancer brain metastases. Cancer Research, 67(4), 1472–1486.  https://doi.org/10.1158/0008-5472.CAN-06-3137.CrossRefGoogle Scholar
  69. 69.
    White, N. M., Newsted, D. W., Masui, O., Romaschin, A. D., Siu, K. W., & Yousef, G. M. (2014). Identification and validation of dysregulated metabolic pathways in metastatic renal cell carcinoma. Tumour Biology, 35(3), 1833–1846.  https://doi.org/10.1007/s13277-013-1245-6.CrossRefGoogle Scholar
  70. 70.
    Piskounova, E., Agathocleous, M., Murphy, M. M., Hu, Z., Huddlestun, S. E., Zhao, Z., Leitch, A. M., Johnson, T. M., DeBerardinis, R. J., & Morrison, S. J. (2015). Oxidative stress inhibits distant metastasis by human melanoma cells. Nature, 527(7577), 186–191.  https://doi.org/10.1038/nature15726.CrossRefGoogle Scholar
  71. 71.
    Vucenik, I., Tantivejkul, K., Zhang, Z. S., Cole, K. E., Saied, I., & Shamsuddin, A. M. (1998). IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line. Anticancer Research, 18(6A), 4083–4090.Google Scholar
  72. 72.
    Castillo, M., Smith, J. K., & Kwock, L. (2000). Correlation of myo-inositol levels and grading of cerebral astrocytomas. AJNR. American Journal of Neuroradiology, 21(9), 1645–1649.Google Scholar
  73. 73.
    Garber, K. (2004). Energy boost: the Warburg effect returns in a new theory of cancer. Journal of the National Cancer Institute, 96(24), 1805–1806.  https://doi.org/10.1093/jnci/96.24.1805.CrossRefGoogle Scholar
  74. 74.
    Ptitsyn, A. A., Weil, M. M., & Thamm, D. H. (2008). Systems biology approach to identification of biomarkers for metastatic progression in cancer. BMC Bioinformatics, 9(Suppl 9), S8.  https://doi.org/10.1186/1471-2105-9-S9-S8.CrossRefGoogle Scholar
  75. 75.
    Yan, J. A., Xiao, H., Ji, H. X., Shen, W. H., Zhou, Z. S., Song, B., Chen, Z. W., & Li, W. B. (2010). Cathepsin L is associated with proliferation and clinical outcome of urothelial carcinoma of the bladder. The Journal of International Medical Research, 38(6), 1913–1922.  https://doi.org/10.1177/147323001003800604.CrossRefGoogle Scholar
  76. 76.
    Zhang, D., Fei, Q., Li, J., Zhang, C., Sun, Y., Zhu, C., Wang, F., & Sun, Y. (2016). 2-Deoxyglucose reverses the promoting effect of insulin on colorectal cancer cells in vitro. PLoS One, 11(3), e0151115.  https://doi.org/10.1371/journal.pone.0151115.CrossRefGoogle Scholar
  77. 77.
    Feinberg, A. P., & Tycko, B. (2004). The history of cancer epigenetics. Nature Reviews. Cancer, 4(2), 143–153.  https://doi.org/10.1038/nrc1279.CrossRefGoogle Scholar
  78. 78.
    Ruivo, C. F., Adem, B., Silva, M., & Melo, S. A. (2017). The biology of Cancer exosomes: Insights and new perspectives. Cancer Research, 77(23), 6480–6488.  https://doi.org/10.1158/0008-5472.CAN-17-0994.CrossRefGoogle Scholar
  79. 79.
    Hoshino, A., Costa-Silva, B., Shen, T. L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., Molina, H., Kohsaka, S., di Giannatale, A., Ceder, S., Singh, S., Williams, C., Soplop, N., Uryu, K., Pharmer, L., King, T., Bojmar, L., Davies, A. E., Ararso, Y., Zhang, T., Zhang, H., Hernandez, J., Weiss, J. M., Dumont-Cole, V. D., Kramer, K., Wexler, L. H., Narendran, A., Schwartz, G. K., Healey, J. H., Sandstrom, P., Jørgen Labori, K., Kure, E. H., Grandgenett, P. M., Hollingsworth, M. A., de Sousa, M., Kaur, S., Jain, M., Mallya, K., Batra, S. K., Jarnagin, W. R., Brady, M. S., Fodstad, O., Muller, V., Pantel, K., Minn, A. J., Bissell, M. J., Garcia, B. A., Kang, Y., Rajasekhar, V. K., Ghajar, C. M., Matei, I., Peinado, H., Bromberg, J., & Lyden, D. (2015). Tumour exosome integrins determine organotropic metastasis. Nature, 527(7578), 329–335.  https://doi.org/10.1038/nature15756.CrossRefGoogle Scholar
  80. 80.
    Perrin, S. (2014). Preclinical research: Make mouse studies work. Nature, 507(7493), 423–425.  https://doi.org/10.1038/507423a.CrossRefGoogle Scholar
  81. 81.
    Jacques, C., Renema, N., Lezot, F., Ory, B., Walkley, C. R., Grigoriadis, A. E., & Heymann, D. (2018). Small animal models for the study of bone sarcoma pathogenesis: Characteristics, therapeutic interests and limitations. Journal of Bone Oncology, 12, 7–13.  https://doi.org/10.1016/j.jbo.2018.02.004.CrossRefGoogle Scholar
  82. 82.
    Wagner, F., Holzapfel, B. M., Thibaudeau, L., Straub, M., Ling, M. T., Grifka, J., Loessner, D., Lévesque, J. P., & Hutmacher, D. W. (2016). A validated preclinical animal model for primary bone tumor research. The Journal of Bone and Joint Surgery. American Volume, 98(11), 916–925.  https://doi.org/10.2106/JBJS.15.00920.CrossRefGoogle Scholar
  83. 83.
    Guiho, R., Biteau, K., Grisendi, G., Chatelais, M., Brion, R., Taurelle, J., et al. (2018). In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factor-related apoptosis inducing ligand in osteosarcoma pre-clinical models. Cytotherapy.  https://doi.org/10.1016/j.jcyt.2018.06.013.
  84. 84.
    Wagner, F., Holzapfel, B. M., McGovern, J. A., Shafiee, A., Baldwin, J. G., Martine, L. C., Lahr, C. A., Wunner, F. M., Friis, T., Bas, O., Boxberg, M., Prodinger, P. M., Shokoohmand, A., Moi, D., Mazzieri, R., Loessner, D., & Hutmacher, D. W. (2018). Humanization of bone and bone marrow in an orthotopic site reveals new potential therapeutic targets in osteosarcoma. Biomaterials, 171, 230–246.  https://doi.org/10.1016/j.biomaterials.2018.04.030.CrossRefGoogle Scholar
  85. 85.
    Jeys, L. M., Grimer, R. J., Carter, S. R., Tillman, R. M., & Abudu, A. (2007). Post operative infection and increased survival in osteosarcoma patients: Are they associated? Annals of Surgical Oncology, 14(10), 2887–2895.  https://doi.org/10.1245/s10434-007-9483-8.CrossRefGoogle Scholar
  86. 86.
    Tuohy, J. L., Lascelles, B. D., Griffith, E. H., & Fogle, J. E. (2016). Association of canine osteosarcoma and monocyte phenotype and chemotactic function. Journal of Veterinary Internal Medicine, 30(4), 1167–1178.  https://doi.org/10.1111/jvim.13983.CrossRefGoogle Scholar
  87. 87.
    Goldsby, R. E., Fan, T. M., Villaluna, D., Wagner, L. M., Isakoff, M. S., Meyer, J., Lor Randall, R., Lee, S., Kim, G., Bernstein, M., Gorlick, R., Krailo, M., & Marina, N. (2013). Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: A report from the Children’s Oncology Group. European Journal of Cancer, 49(10), 2384–2391.  https://doi.org/10.1016/j.ejca.2013.03.018.CrossRefGoogle Scholar
  88. 88.
    Ory, B., Heymann, M. F., Kamijo, A., Gouin, F., Heymann, D., & Redini, F. (2005). Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma-bearing mice. Cancer, 104(11), 2522–2529.  https://doi.org/10.1002/cncr.21530.CrossRefGoogle Scholar
  89. 89.
    Whelan, J. S., & Davis, L. E. (2018). Osteosarcoma, chondrosarcoma, and chordoma. Journal of Clinical Oncology, 36(2), 188–193.  https://doi.org/10.1200/JCO.2017.75.1743.CrossRefGoogle Scholar
  90. 90.
    Siegel, R. L., Miller, K. D., & Jemal, A. (2017). Cancer statistics, 2017. CA: a Cancer Journal for Clinicians, 67(1), 7–30.  https://doi.org/10.3322/caac.21387.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Dylan C. Dean
    • 1
  • Shen Shen
    • 1
    • 2
  • Francis J. Hornicek
    • 1
  • Zhenfeng Duan
    • 1
    Email author
  1. 1.Department of Orthopaedic Surgery, Sarcoma Biology LaboratoryDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Precision Medicine CenterThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Personalised recommendations