[en] Osteopontin (OPN), a member of the SIBLING (Small Integrin-Binding LIgand N-linked Glycoprotein) family, is overexpressed in human glioblastoma. Higher levels of OPN expression correlate with increased tumor grade and enhanced migratory capacity of tumor cells. Based on these observations, we explored the possibility that knocking down OPN expression in glioblastoma cells could exert an anti-tumoral activity using an avian in vivo glioblastoma model that mimics closely human gliobastoma. Human U87-MG glioma cells transfected with specific anti-OPN small interfering RNAs (siRNAs) were grafted onto the chicken chorio-allantoic membrane (CAM). OPN-deficient U87-MG cells gave rise to tumors that were significantly smaller than tumors formed from untransfected cells (paired t-test, p<0.05). Accordingly, the amount of proliferating cells in OPN-deficient tumors showed a six-fold reduction when compared to control tumors. However, OPN inhibition did not affect significantly tumor-associated angiogenesis. In vitro, OPN-silenced U87-MG and U373-MG cells showed decreased motility and migration. This is the first demonstration that OPN inhibition blocks glioma tumor growth, making this invasion-related protein an attractive target for glioma therapy. (c) 2009 UICC.
Lamour, Virginie ; Université de Liège - ULiège > Centre facultaire de rech. en cancérologie expérimentale
Le Mercier, M.
Lefranc, F.
Hagedorn, M.
Javerzat, S.
Bikfalvi, A.
Kiss, R.
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire - GIGA-R : Labo de recherche sur les métastases
Bellahcene, Akeila ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Language :
English
Title :
Selective osteopontin knockdown exerts anti-tumoral activity in a human glioblastoma model.
Publication date :
2010
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
Wiley Liss, Inc., New York, United States - New York
Volume :
126
Pages :
1797-1805
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Lefranc, F., Brotchi, J., Kiss, R., Possible future issues in the treatment of glioblastomas: Special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis (2005) Journal of Clinical Oncology, 23 (10), pp. 2411-2422. , DOI 10.1200/JCO.2005.03.089
Fisher, L.W., Torchia, D.A., Fo.hr B, Young MF, Fedarko NS. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin (2001) Biochem Biophys Res Commun, 280, pp. 460-465
Bellahcene, A., Castronovo, V., Ogbureke, K.U.E., Fisher, L.W., Fedarko, N.S., Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): Multifunctional proteins in cancer (2008) Nature Reviews Cancer, 8 (3), pp. 212-226. , DOI 10.1038/nrc2345, PII NRC2345
Coppola, D., Szabo, M., Boulware, D., Muraca, P., Alsarraj, M., Chambers, A.F., Yeatman, T.J., Correlation of Osteopontin Protein Expression and Pathological Stage across a Wide Variety of Tumor Histologies (2004) Clinical Cancer Research, 10 (1 I), pp. 184-190. , DOI 10.1158/1078-0432.CCR-1405-2
Saitoh, Y., Kuratsu, J., Takeshima, H., Yamamoto, S., Ushio, Y., Expression of osteopontin in human glioma. Its correlation with the malignancy (1995) Lab Invest, 72, pp. 55-63
Gunnersen, J.M., Spirkoska, V., Smith, P.E., Danks, R.A., Tan, S.S., Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression (2000) GUa, 32, pp. 146-154
Jang, T., Savarese, T., Low, H.P., Kim, S., Vogel, H., Lapointe, D., Duong, T., Recht, L., Osteopontin expression in intratumoral astrocytes marks tumor progression in gliomas induced by prenatal exposure to N-eťhyl-N-nitrosourea (2006) Am J Pathol, 168, pp. 1676-1685
Jang, T., Sathy, B., Hsu, Y.H., Merchant, M., Recht, B., Chang, C., Recht, L., A distinct phenotypic change in gliomas at the time of magnetic resonance imaging detection (2008) J Neurosurg, 108, pp. 782-790
D'Abaco, G.M., Kaye, A.H., Integrins: Molecular determinants of glioma invasion (2007) J Clin Neurosa, 14, pp. 1041-1048
Hagedorn, M., Javerzat, S., Gilges, D., Meyre, A., De Lafarge, B., Eichmann, A., Bikfalvi, A., Accessing key steps of human tumor progression in vivo by using an avian embryo model (2005) Proceedings of the National Academy of Sciences of the United States of America, 102 (5), pp. 1643-1648. , DOI 10.1073/pnas.0408622102
Chaplet, M., Detry, C., Deroanne, C., Fisher, L.W., Castronovo, V., Beiiahcene, A., Zoledronic acid up-regulates bone sialoprotein expression in osteoblastic cells through Rho GTPase inhibition (2004) Biochem J., 384, pp. 591-598
Ceietti, A., Testa, D., Staibano, S., Merolla, F., Guarino, V., Castellone, M.D., Iovine, R., Melillo, R.M., Overexpression of the cytokine osteopontin identifies aggressive laryngeal squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness (2005) Clin Cancer Res, 11, pp. 8019-8027
Saidi, A., Javerzat, S., Bellahcene, A., De Vos, J., Bello, L., Castronovo, V., Deprez, M., Hagedorn, M., Experimental anti-angiogenesis causes upregulation of genes associated with poor survival in glioblastoma (2008) International Journal of Cancer, 122 (10), pp. 2187-2198. , DOI 10.1002/ijc.23313
Goldberg, L., Kloog, Y., A Ras inhibitor tilts the balance between Rac and Rho and blocks phosphatidylinositol 3-kinase-dependent glioblastoma cell migration (2006) Cancer Research, 66 (24), pp. 11709-11717. , DOI 10.1158/0008-5472.CAN-06-1878
Kon, S., Maeda, M., Segawa, T., Hagiwara, Y., Horikoshi, Y., Chikuma, S., Tanaka, K., Uede, T., Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms (2000) Journal of Cellular Biochemistry, 77 (3), pp. 487-498. , DOI 10.1002/(SICI)1097-4644(20000601)77:3<487::AID-JCB13>3.0.CO
2-8
Bautista, D.S., Xuan, J.-W., Hota, C., Chambers, A.F., Harris, J.F., Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin (1994) Journal of Biological Chemistry, 269 (37), pp. 23280-23285
Christensen, B., Nielsen, M.S., Haselmann, K.F., Petersen, T.E., Sorensen, E.S., Post-translationally modified residues of native human osteopontin are located in clusters: Identification of 36 phosphorylation and five O-glycosylation sites and their biological implications (2005) Biochemical Journal, 390 (1), pp. 285-292. , DOI 10.1042/BJ20050341
Rangaswami, H., Bulbule, A., Kundu, G.C., Osteopontin: Role in cell signaling and cancer progression (2006) Trends in Cell Biology, 16 (2), pp. 79-87. , DOI 10.1016/j.tcb.2005.12.005, PII S0962892405003132
Tuck, A.B., Chambers, A.F., Allan, A.L., Osteopontin overexpression in breast cancer: Knowledge gained and possible implications for clinical management (2007) J Cell Biochem
Chakraborty, G., Jain, S., Pat.il TV, Kundu GC. Down-Regulation of Osteopontin Attenuates Breast Tumor Progression in vivo (2008) J Cell Mol Med, 6, pp. 2305-2318
Shevde, L.A., Samant, R.S., Paik, J.C., Metge, B.J., Chambers, A.F., Casey, G., Frost, A.R., Welch, D.R., Osteopontin knockdown suppresses tumorigenicity of human metastatic breast carcinoma, MDA-MB-435 (2006) Clinical and Experimental Metastasis, 23 (2), pp. 123-133. , DOI 10.1007/s10585-006-9013-2
Sun, B.S., Dong, Q.Z., Ye, Q.H., Sun, H.J., Jia, H.L., Zhu, X.Q., Liu, D.Y., Qin, L.X., Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma (2008) Hepatology, 48, pp. 1834-1842
Suzuki, M., Mose, E., Galloy, C., Tarin, D., Osteopontin gene expression determines spontaneous metastatic performance of orthotopic human breast cancer xenografts (2007) American Journal of Pathology, 171 (2), pp. 682-692. , DOI 10.2353/ajpath.2007.070232
Wai, P.Y., Mi, Z., Guo, H., Sarraf-Yazdi, S., Gao, C., Wei, J., Marroquin, C.E., Kuo, P.C., Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis (2005) Carcinogenesis, 26 (4), pp. 741-751. , DOI 10.1093/carcin/bgi027
Selkirk, S.M., Morrow, J., Barone, T.A., Hoffer, A., Lock, J., Dechant, A., Mangla, S., Miller, R.H., Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal (2007) J Neurooncol, 86, pp. 285-296
Takahashi, F., Akutagawa, S., Fukumoto, H., Tsukiyama, S., Ohe, Y., Takahashi, K., Fukuchi, Y., Nishio, K., Osteopontin induces angiogenesis of murine neuroblastoma cells in mice (2002) International Journal of Cancer, 98 (5), pp. 707-712. , DOI 10.1002/ijc.10261
Leali, D., Moroni, E., Bussolino, F., Presta, M., Osteopontin overexpression inhibits in vitro re-endothelialization via integrin engagement (2007) Journal of Biological Chemistry, 282 (27), pp. 19676-19684. , http://www.jbc.org/cgi/reprint/282/27/19676, DOI 10.1074/jbc.M606938200
Kuijpers, T.W., Mul, E.P.J., Blom, M., Kovach, N.L., Gaeta, F.C.A., Tollefson, V., Elices, M.J., Harlan, J.M., Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration (1993) Journal of Experimental Medicine, 178 (1), pp. 279-284
Gupton, S.L., Waterman-Storer, C.M., Spatiotemporal feedback, between actomyosin and focal-adhesion systems optimizes rapid cell migration (2006) Cell, 125, pp. 1361-1374
Bellail, A.C., Hunter, S.B., Brat, D.J., Tan, C., Van Meir, E.G., Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion (2004) International Journal of Biochemistry and Cell Biology, 36 (6), pp. 1046-1069. , DOI 10.1016/j.biocel.2004.01.013, PII S1357272504000214
Kim, M.-S., Park, M.-J., Moon, E.-J., Kim, S.-J., Lee, C.-H., Yoo, H., Shin, S.-H., Lee, S.-H., Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells (2005) Cancer Research, 65 (3), pp. 686-691
Merzak, A., Koocheckpour, S., Pilkington, G.J., CD44 mediates human glioma cell adhesion and invasion in vitro (1994) Cancer Research, 54 (15), pp. 3988-3992
Rao, J.S., Molecular mechanisms of glioma invasiveness: The role of proteases (2003) Nat Rev Cancer, 3, pp. 489-501
Matusan-Ilijas, K., Behrem, S., Jonjic, N., Zarkovic, K., Lucin, K., Osteopontin expression correlates with angiogenesis and survival in malignant astrocytoma (2008) Pathol Oncol Res, 14, pp. 293-298
Cheng, S.-Y., Huang, H.-J.S., Nagane, M., Ji, X.-D., Wang, D., Shih, C.C.-Y., Arap, W., Cavenee, W.K., Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor (1996) Proceedings of the National Academy of Sciences of the United States of America, 93 (16), pp. 8502-8507. , DOI 10.1073/pnas.93.16.8502
Senger, D.R., Ledbetter, S.R., Claffey, K.P., Papadopoulos-Sergiou, A., Perruzzi, C.A., Detmar, M., Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the α(v)β3 integrin, osteopontin, and thrombin (1996) American Journal of Pathology, 149 (1), pp. 293-305
Mathupala, S.P., Guthikonda, M., Sloan, A.E., RNAi based approaches to the treatment of malignant glioma (2006) Technology in Cancer Research and Treatment, 5 (3), pp. 261-269
Zhang, Y., Zhang, Y.-F., Bryant, J., Charles, A., Boado, R.J., Pardridge, W.M., Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer (2004) Clinical Cancer Research, 10 (11), pp. 3667-3677. , DOI 10.1158/1078-0432.CCR-03-0740
Giussani, C., Carrabba, G., Pluderi, M., Lucini, V., Pannacci, M., Caronzolo, D., Costa, F., Bello, L., Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in vivo (2003) Cancer Research, 63 (10), pp. 2499-2505
Mercier, M.L., Mathieu, V., Haibe-Kains, B., Bontempi, G., Mijatovic, T., Decaestecker, C., Kiss, R., Lefranc, F., Knocking down galectin 1 in human Hs683 glioblastoma cells impairs both angiogenesis and endoplasmic reticulum stress responses (2008) Journal of Neuropathology and Experimental Neurology, 67 (5), pp. 456-469. , DOI 10.1097/NEN.0b013e318170f892