Skip to main content
NCBI home page
Cellular & Molecular Biology Letters logoLink to Cellular & Molecular Biology Letters
. 2007 Oct 19;13(1):11–19. doi: 10.2478/s11658-007-0031-0

The inhibition of in vivo tumorigenesis of osteosarcoma (OS)-732 cells by antisense human osteopontin RNA

Si-Jin Liu 1,6,✉, Dao-Qiang Zhang 2, Xiu-Mei Sui 2, Lin Zhang 3, Zi-Wei Cai 4, Li-Qiu Sun 4, Ya-Jun Liu 5, Yan Xue 5, Guo-Fa Hu 1
PMCID: PMC6275891  PMID: 17952379

Abstract

Osteopontin (OPN) is a secreted, non-collagenous, sialic acid-rich protein which functions by mediating cell-matrix interactions and cellular signaling via binding with integrins and CD44 receptors. An increasing number of studies have shown that OPN plays an important role in controlling cancer progression and metastasis. OPN was found to be expressed in many human cancer types, and in some cases, its over-expression was shown to be directly associated with poor patient prognosis. In vitro cancer cell line and animal model studies have clearly indicated that OPN can function in regulating the cell signaling that ultimately controls the oncogenic potential of various cancers. Previous studies in our laboratory demonstrated that OPN is highly expressed in human osteosarcoma (OS) cell line OS-732. In this study, we successfully reduced the tumorigenecity of OS-732 cells xenotransplanted into nude mice, using the antisense human OPN (hOPN) RNA expression vector.

Key words: Osteopontin, Osteosarcoma, Antisense RNA

Full Text

The Full Text of this article is available as a PDF (530.9 KB).

Abbreviations used

hOPN

human OPN

OPN

osteopontin

OS

osteosarcoma

References

  • 1.Furger K.A., Menon R.K., Tuck A.B., Bramwell V.H., Chambers A.F. The functional and clinical roles of osteopontin in cancer and metastasis. Curr. Mol. Med. 2001;1:621–632. doi: 10.2174/1566524013363339. [DOI] [PubMed] [Google Scholar]
  • 2.Rittling S.R., Chambers A.F. Role of osteopontin in tumour progression. Br. J. Cancer. 2004;90:1877–1881. doi: 10.1038/sj.bjc.6601839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Rangaswami H., Bulbule A., Kundu G.C. Osteopontin: role in cell signaling and cancer progression. Trends Cell. Biol. 2006;16:79–87. doi: 10.1016/j.tcb.2005.12.005. [DOI] [PubMed] [Google Scholar]
  • 4.Weber G.F. The metastasis gene osteopontin: a candidate target for cancer therapy. Biochim. Biophys. Acta. 2001;1552:61–85. doi: 10.1016/s0304-419x(01)00037-3. [DOI] [PubMed] [Google Scholar]
  • 5.El-Tanani M.K., Campbell F.C., Kurisetty V., Jin D., McCann M., Rudland P.S. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev. 2006;17:463–474. doi: 10.1016/j.cytogfr.2006.09.010. [DOI] [PubMed] [Google Scholar]
  • 6.Fedarko N.S., Jain A., Karadag A., Fisher L.W. Three small integrin binding ligand N-linked glycoproteins (SIBLINGs) bind and activate specific matrix metalloproteinases. FASEB. J. 2004;18:734–736. doi: 10.1096/fj.03-0966fje. [DOI] [PubMed] [Google Scholar]
  • 7.Haqq C., Nosrati M., Sudilovsky D., Crothers J., Khodabakhsh D., Pulliam B.L., Federman S., Miller J.R., Allen R.E., Singer M.I., Leong S.P., Ljung B.M., Sagebiel R.W., Kashani-Sabet M. The gene expression signatures of melanoma progression. Proc. Natl. Acad. Sci. USA. 2005;102:6092–6097. doi: 10.1073/pnas.0501564102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Chakraborty G., Jain S., Behera R., Ahmed M., Sharma P., Kumar V., Kundu G.C. The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis. Curr. Mol. Med. 2006;6:819–830. doi: 10.2174/156652406779010803. [DOI] [PubMed] [Google Scholar]
  • 9.Wai P.Y., Kuo P.C. The role of Osteopontin in tumor metastasis. J. Surg. Res. 2004;121:228–241. doi: 10.1016/j.jss.2004.03.028. [DOI] [PubMed] [Google Scholar]
  • 10.Gardner H.A., Berse B., Senger D.R. Specific reduction in osteopontin synthesis by antisense RNA inhibits the tumorigenicity of transformed Rat1 fibroblasts. Oncogene. 1994;9:2321–2326. [PubMed] [Google Scholar]
  • 11.Denhardt D. Osteopontin expression correlates with melanoma invasion. J. Invest. Dermatol. 2005;124:16–18. doi: 10.1111/j.0022-202X.2005.23708.x. [DOI] [PubMed] [Google Scholar]
  • 12.Wai P.Y., Mi Z., Guo H., Sarraf-Yazdi S., Gao C., Wei J., Marroquin C.E., Clary B., Kuo P.C. Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis. Carcinogenesis. 2005;26:741–751. doi: 10.1093/carcin/bgi027. [DOI] [PubMed] [Google Scholar]
  • 13.Wu Y., Denhardt D.T., Rittling S.R. Osteopontin is required for full expression of the transformed phenotype by the ras oncogene. Br. J. Cancer. 2000;83:156–163. doi: 10.1054/bjoc.2000.1200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Ek E.T., Dass C.R., Choong P.F. Commonly used mouse models of osteosarcoma. Crit. Rev. Oncol. Hematol. 2006;60:1–8. doi: 10.1016/j.critrevonc.2006.03.006. [DOI] [PubMed] [Google Scholar]
  • 15.Greene F.L. AJCC Cancer Staging Manual. New York: Springer-Verlag; 2002. [Google Scholar]
  • 16.Liu S.J., Hu G.F., Liu Y.J., Liu S.G., Gao H., Zhang C.S., Wei Y.Y., Xue Y., Lao W.D. The Effect of Human Osteopontin on the Proliferation. Transmigration and Expression of Matrix Metallproteinase-2 and 9 of Osteosarcoma Cells in vitro. Chin. Med. J. (Engl.) 2004;117:235–240. [PubMed] [Google Scholar]
  • 17.Liu S.G., Wei Y.Y., Hu G.F., Gao H., Liu S.J., Lao W.D. An expression profile of human α-lactalbumin in the milk of transgenic mouse. Science In. Chin, Series C-Life Sciences. 2004;47:197–202. doi: 10.1007/BF03182763. [DOI] [PubMed] [Google Scholar]
  • 18.Porchet N., Aubert J.P. Northern blot analysis of large mRNAs. Methods Mol. Biol. 2000;125:305–312. doi: 10.1385/1-59259-048-9:305. [DOI] [PubMed] [Google Scholar]
  • 19.Cioffi C.L., Garay M., Johnston J.F., McGraw K., Boggs R.T., Hreniuk D., Monia B.P. Selective inhibition of A-Raf and C-Raf mRNA expression by antisense oligodeoxynucleotides in rat vascular smooth muscle cells: role of A-Raf and C-Raf in serum-induced proliferation. Mol. Pharmacol. 1997;51:383–389. [PubMed] [Google Scholar]
  • 20.Li F., Altieri D.C. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res. 1999;59:3143–3151. [PubMed] [Google Scholar]
  • 21.Ru K., Schmitt S., James W.I., Wang J.H. Growth inhibition and antimetastatic effect of antisense poly-DNP-RNA on human breast cancer cells. Oncol. Res. 1999;11:505–512. [PubMed] [Google Scholar]
  • 22.Ulanova M., Schreiber A.D., Befus A.D. The future of antisense oligonucleotides in the treatment of respiratory diseases. BioDrugs. 2006;20:1–11. doi: 10.2165/00063030-200620010-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Reed J.C., Cuddy M., Haldar S., Croce C., Nowell P., Makover D., Bradley K. BCL2-mediated tumorigenicity of a human T-lymphoid cell line: synergy with MYC and inhibition by BCL2 antisense. Proc. Natl. Acad. Sci. USA. 1990;87:3660–3664. doi: 10.1073/pnas.87.10.3660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Zhang X., Chen Z., Chen Y., Tong T. Delivering antisense telomerase RNA by a hybrid adenovirus/ adeno-associated virus significantly suppresses the malignant phenotype and enhances cell apoptosis of human breast cancer cells. Oncogene. 2003;22:2405–2416. doi: 10.1038/sj.onc.1206317. [DOI] [PubMed] [Google Scholar]
  • 25.Scotlandi K., Avnet S., Benini S., Manara M.C., Serra M., Cerisano V., Perdichizzi S., Lollini P.L., De Giovanni C., Landuzzi L., Picci P. Expression of an IGF-I receptor dominant negative mutant induces apoptosis, inhibits tumorigenesis and enhances chemosensitivity in Ewing’s sarcoma cells. Int. J. Cancer. 2002;101:11–16. doi: 10.1002/ijc.10537. [DOI] [PubMed] [Google Scholar]
  • 26.Resnicoff M., Sell C., Rubini M., Coppola D., Ambrose D., Baserga R., Rubin R. Rat glioblastoma cells expressing an antisense RNA to the insulin-like growth factor-1 (IGF-1) receptor are nontumorigenic and induce regression of wild-type tumors. Cancer Res. 1994;54:2218–2222. [PubMed] [Google Scholar]
  • 27.Oku T., Tjuvajev J.G., Miyagawa T., Sasajima T., Joshi A., Joshi R., Finn R., Claffey K.P., Blasberg R.G. Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts. Cancer Res. 1998;58:4185–4192. [PubMed] [Google Scholar]
  • 28.Belletti B., Ferraro P., Arra C., Baldassarre G., Bruni P., Staibano S., De Rosa G., Salvatore G., Fusco A., Persico M.G., Viglietto G. Modulation of in vivo growth of thyroid tumor-derived cell lines by sense and antisense vascular endothelial growth factor gene. Oncogene. 1999;18:4860–4869. doi: 10.1038/sj.onc.1202869. [DOI] [PubMed] [Google Scholar]
  • 29.He Y., Zeng Q., Drenning S.D., Melhem M.F., Tweardy D.J., Huang L., Grandis J.R. Inhibition of human squamous cell carcinoma growth in vivo by epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. J. Natl. Cancer Inst. 1998;90:1080–1087. doi: 10.1093/jnci/90.14.1080. [DOI] [PubMed] [Google Scholar]
  • 30.Huber L.C., Distler O., Gay R.E., Gay S. Antisense strategies in degenerative joint diseases: sense or nonsense? Adv. Drug Deliv. Rev. 2006;58:285–299. doi: 10.1016/j.addr.2006.01.010. [DOI] [PubMed] [Google Scholar]
  • 31.Friedrich I., Shir A., Klein S., Levitzki A. RNA molecules as anticancer agents. Semin. Cancer Biol. 2004;14:223–230. doi: 10.1016/j.semcancer.2004.04.001. [DOI] [PubMed] [Google Scholar]
  • 32.Liu S.J., Hu G.F., Liu S.G., Lao W.D. Functional analysis of human osteopontin (hOPN) in cellular proliferation. High. Technol. Lett. 2003;13:25–28. [Google Scholar]
  • 33.Gleave M.E., Monia B.P. Antisense therapy for cancer. Nat. Rev. Cancer. 2005;5:468–479. doi: 10.1038/nrc1631. [DOI] [PubMed] [Google Scholar]
  • 34.Folini M., Zaffaroni N. Targeting telomerase by antisense-based approaches: perspectives for new anti-cancer therapies. Curr. Pharm. Des. 2005;11:1105–1117. doi: 10.2174/1381612053507558. [DOI] [PubMed] [Google Scholar]
  • 35.Benimetskaya L., Stein C.A. Antisense therapy: recent advances and relevance to prostate cancer. Clin. Prostate Cancer. 2002;1:20–30. doi: 10.3816/cgc.2002.n.003. [DOI] [PubMed] [Google Scholar]
  • 36.Wacheck V., Zangemeister-Wittke U. Antisense molecules for targeted cancer therapy. Crit. Rev. Oncol. Hematol. 2006;59:65–73. doi: 10.1016/j.critrevonc.2005.10.004. [DOI] [PubMed] [Google Scholar]

Articles from Cellular & Molecular Biology Letters are provided here courtesy of BMC

RESOURCES