Abstract
Osteosarcoma is a malignant tumour arising from transformed cells of mesenchymal origin. It is the most common malignant bone tumour of the teenage years. Because there is no prognostic marker available except metastasis and because molecular therapy has not yet been developed in osteosarcoma, the search continues for useful biomarkers and effective molecular targets for this disease.
Midkine strongly affects cell proliferation and clinical prognosis in osteosarcoma and other tumour cells. There is a correlation between the levels of midkine expressed in osteosarcoma cells and the prognosis. Treatment with anti-midkine molecules causes apparent growth inhibition in osteosarcoma cells in vitro and in vivo, suggesting that midkine would be a good target for therapy. However, the precise mechanism of tumour growth and invasion in osteosarcoma is still unclear. What receptor mediates the growth signalling of midkine in osteosarcoma and whether midkine accelerates metastasis remains to be determined. Clarifying this process will further the development of molecular therapy for patients with osteosarcoma.
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References
Longhi A, Errani C, De Paolis M et al (2006) Primary bone osteosarcoma in the pediatric age: state of the art. Cancer Treat 32:423–436
Geller DS, Gorlick R (2010) Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol 8:705–718
Houghton PJ, Morton CL, Kolb EA et al (2008) Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer 50:799–805
Erkizan HV, Uversky VN, Toretsky JA (2010) Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing’s sarcoma. Clin Cancer Res 16:4077–4083
Ladanyi M, Antonescu CR, Leung DH et al (2002) Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res 62:135–140
Lim G, Karaskova J, Beheshti B et al (2005) An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma. Genes Chromosomes Cancer 42:392–403
Selvarajah S, Yoshimoto M, Maire G et al (2007) Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. Cancer Genet Cytogenet 179:52–61
Miller CW, Aslo A, Tsay C et al (1990) Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer Res 50:7950–7954
Chandar N, Billig B, McMaster J et al (1992) Inactivation of p53 gene in human and murine osteosarcoma cells. Br J Cancer 65:208–214
B-i W, Toguchida J, Shimizu T et al (1994) Mutation spectrum of the retinoblastoma gene in osteosarcoma. Cancer Res 54:3042–3048
Porter DE, Holden ST, Steel CM et al (1992) A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families. J Bone Joint Surg Br 74:883–886
Berman SD, Calo E, Landman AS et al (2008) Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci USA 105:11851–11856
Walkley CR, Qudsi R, Sankaran VG et al (2008) Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev 22:1662–1676
Kaname T, Kadomatsu K, Aridome K et al (1996) The expression of truncated MK in human tumors. Biochem Biophys Res Commun 219:256–260
Miyashiro I, Kaname T, Shin E et al (1997) Midkine expression in human breast cancers: expression of truncated form. Breast Cancer Res Treat 43:1–6
Aridome K, Takao S, Kaname T et al (1998) Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas. Br J Cancer 78:472–477
Muramatsu T (2010) Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases. Proc Jpn Acad Ser B Phys Biol Sci 86:410–425
Hausser H-J, Brenner RE (2005) Phenotypic instability of Saos-2 cells in long-term culture. Biochem Biophys Res Commun 333:216–222
Maehara H, Kaname T, Yanagi K et al (2007) Midkine as a novel target for antibody therapy in osteosarcoma. Biochem Biophys Res Commun 358:757–762
Yu L, Ugai S, O-Wang J et al (2003) Cell growth- and P53-dependent transcriptional activity of the midkine promoter confers suicide gene expression in tumor cells. Oncol Rep 10:1301–1305
Sakaguchi N, Muramatsu H, Ichihara-Tanaka K et al (2003) Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons. Neurosci Res 45:219–224
Jin Z, Lahat G, Korchin B et al (2008) Midkine enhances soft-tissue sarcoma growth: a possible novel therapeutic target. Clin Cancer Res 14:5033–5042
Shor AC, Keschman EA, Lee FY et al (2007) Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival. Cancer Res 67:2800–2808
Hingorani P, Zhang W, Gorlick R et al (2009) Inhibition of Src phosphorylation alters metastatic potential of osteosarcoma in vitro but not in vivo. Clin Cancer Res 15:3416–3422
Frame MC (2002) Src in cancer: deregulation and consequences for cell behavior. Biochim Biophys Acta 1602:114–130
Basappa MS, Sugahara KN et al (2009) Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells. Glycobiology 19:735–742
Tsutsui J, Kadomatsu K, Matsubara S et al (1993) A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms’ tumor and other human carcinomas. Cancer Res 53:1281–1285
O’Brien T, Cranston D, Fuggle S et al (1996) The angiogenic factor midkine is expressed in bladder cancer, and overexpression correlates with a poor outcome in patients with invasive cancers. Cancer Res 56:2515–2518
Muramatsu H, Song XJ, Koide N et al (1996) Enzyme-linked immunoassay for midkine, and its application to evaluation of midkine levels in developing mouse brain and sera from patients with hepatocellular carcinomas. J Biochem 119:1171–1175
Ikematsu S, Yano A, Aridome K et al (2000) Serum midkine levels are increased in patients with various types of carcinomas. Br J Cancer 83:701–706
Ikematsu S, Nakagawara A, Nakamura Y et al (2008) Plasma midkine level is a prognostic factor for human neuroblastoma. Cancer Sci 99:2070–2074
Muramatsu H, Shirahama H, Yonezawa S et al (1993) Midkine, a retinoic acid-inducible growth/differentiation factor: immunochemical evidence for the function and distribution. Dev Biol 159:392–402
Takei Y, Kadomatsu K, Goto T et al (2006) Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts. Cancer 107:864–873
Maehara H, Kaname T, Yanagi K et al (2009) Midkine as anti-tumor drugs for osteosarcoma [abstract]. Proc Am Assoc Cancer Res, 1350
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Funding: Grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant-in-Aid for Scientific Research to Tadashi Kaname).
Conflict of interest: None declared.
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Kaname, T., Yanagi, K., Maehara, H. (2012). Osteosarcoma and Midkine. In: Ergüven, M., Muramatsu, T., Bilir, A. (eds) Midkine: From Embryogenesis to Pathogenesis and Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4234-5_27
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DOI: https://doi.org/10.1007/978-94-007-4234-5_27
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