Biopolym. Cell. 2005; 21(2):157-164.
Molecular Biomedicine
Activation of the expression of SPARC gene occuring early in astrocytic glioma progression
1Dmitrenko V. V., 1Shostak K. O., 1Boyko O. I., 1Simirenko O. E., 1Gundorov I. S., 2Khomenko O. V., 2Rozumenko V. D., 2Malisheva T. A., 2Shamaev M. I., 2Zozulya Yu. A., 1Kavsan V. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of Neurosurgery named after A. P. Romodanov, NAMS of Ukraine
    32, Manuilskogo Str., Kyiv, Ukraine, 04050

Abstract

Comparison of gene expression levels in astrocytic gliomas and human normal brain by SAGE revealed SPARC gene among those the expression of which increases most significantly (more than 5-fold, p 0.05). High level of the SPARC gene expression was detected in differentiated astrocytomas as well as in malignant glial tumors. Northern hybridization confirmed the SAGE results and showed that the SPARC gene expression elevated in astrocytomas of grade II-IV as compared to human normal brain. Two SPARC transcripts of about 2 and 3 kb length were detected almost in all the tumour samples. A longer mRNA is synthesized preferentially in tumour cells. The SPARC gene expression changes may play a role in the gliomas invasion and their angiogenesis. SPARC gene seems to be a specific invasion factor in view of our results on substantial enhancement of its expression in the gliomas of different malignancy grades and the corresponding literature data. Since the SPARC expression level is much higher in the tumours of low grades (differentiated astrocytomas) than that in the tumours of high grade (glioblastomas) this gene can not be regarded as a specific marker of increasing tumor aggressiveness.
Keywords: astrocytomas, gliomas, SPARC gene, SAGE, genes expression

References

[1] Rempel SA. Molecular biology of central nervous system tumors. Curr Opin Oncol. 1998;10(3):179-85.
[2] Swaroop A, Hogan BL, Francke U. Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33. Genomics. 1988;2(1):37-47.
[3] Sage EH, Bornstein P. Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin. J Biol Chem. 1991;266(23):14831-4.
[4] Lane TF, Sage EH. The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB J. 1994;8(2):163-73.
[5] Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991;64(2):327-36.
[6] Wewer UM, Albrechtsen R, Fisher LW, Young MF, Termine JD. Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane. Am J Pathol. 1988;132(2):345-55.
[7] Shostak KO, Dmitrenko VV, Garifulin OM, Rozumenko VD, Khomenko OV, Zozulya YA, Zehetner G, Kavsan VM. Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors. J Surg Oncol. 2003;82(1):57-64.
[8] Shostak K, Labunskyy V, Dmitrenko V, Malisheva T, Shamayev M, Rozumenko V, Zozulya Y, Zehetner G, Kavsan V. HC gp-39 gene is upregulated in glioblastomas. Cancer Lett. 2003;198(2):203-10.
[9] Ishii M, Hashimoto S, Tsutsumi S, Wada Y, Matsushima K, Kodama T, Aburatani H. Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis. Genomics. 2000;68(2):136-43.
[10] Rempel SA, Golembieski WA, Ge S, Lemke N, Elisevich K, Mikkelsen T, Gutiérrez JA. SPARC: a signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas. J Neuropathol Exp Neurol. 1998;57(12):1112-21.
[11] Leprini A, Querzé G, Zardi L. Tenascin isoforms: possible targets for diagnosis and therapy of cancer and mechanisms regulating their expression. Perspect Dev Neurobiol. 1994;2(1):117-23. Review.
[12] Xu X, Joh HD, Pin S, Schiller NI, Prange C, Burger PC, Schiller MR. Expression of multiple larger-sized transcripts for several genes in oligodendrogliomas: potential markers for glioma subtype. Cancer Lett. 2001;171(1):67-77.
[13] Matsumoto R, Tada M, Nozaki M, Zhang CL, Sawamura Y, Abe H. Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res. 1998;58(4):609-13.
[14] Zhang D, Paley AJ, Childs G. The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem. 1998;273(29):18086-91.
[15] Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest. 2001;107(9):1049-54.
[16] Sage H, Tupper J, Bramson R. Endothelial cell injury in vitro is associated with increased secretion of an Mr 43,000 glycoprotein ligand. J Cell Physiol. 1986;127(3):373-87.
[17] Sage H, Vernon RB, Decker J, Funk S, Iruela-Arispe ML. Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice. J Histochem Cytochem. 1989;37(6):819-29.
[18] Brekken RA, Sage EH. SPARC, a matricellular protein: at the crossroads of cell-matrix communication. Matrix Biol. 2001;19(8):816-27.
[19] Yan Q, Sage EH. SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem. 1999;47(12):1495-506.
[20] Tremble PM, Lane TF, Sage EH, Werb Z. SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway. J Cell Biol. 1993;121(6):1433-44.
[21] Hasselaar P, Loskutoff DJ, Sawdey M, Sage EH. SPARC induces the expression of type 1 plasminogen activator inhibitor in cultured bovine aortic endothelial cells. J Biol Chem. 1991;266(20):13178-84.
[22] Sage EH. Terms of attachment: SPARC and tumorigenesis. Nat Med. 1997;3(2):144-6.
[23] Rosenblatt S, Bassuk JA, Alpers CE, Sage EH, Timpl R, Preissner KT. Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BM40, SPARC). Biochem J. 1997;324 ( Pt 1):311-9.
[24] Sage EH. Secretion of SPARC by endothelial cells transformed by polyoma middle T oncogene inhibits the growth of normal endothelial cells in vitro. Biochem Cell Biol. 1992;70(7):579-92.
[25] Murphy-Ullrich JE, Lane TF, Pallero MA, Sage EH. SPARC mediates focal adhesion disassembly in endothelial cells through a follistatin-like region and the Ca(2+)-binding EF-hand. J Cell Biochem. 1995;57(2):341-50.
[26] Sage EH, Reed M, Funk SE, Truong T, Steadele M, Puolakkainen P, Maurice DH, Bassuk JA. Cleavage of the matricellular protein SPARC by matrix metalloproteinase 3 produces polypeptides that influence angiogenesis. J Biol Chem. 2003;278(39):37849-57.
[27] Kato Y, Lewalle JM, Baba Y, Tsukuda M, Sakai N, Baba M, Kobayashi K, Koshika S, Nagashima Y, Frankenne F, Noël A, Foidart JM, Hata RI. Induction of SPARC by VEGF in human vascular endothelial cells. Biochem Biophys Res Commun. 2001;287(2):422-6.
[28] Takano T, Hasegawa Y, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K, Hayashi N, Nakamori S, Amino N. Quantitative analysis of osteonectin mRNA in thyroid carcinomas. Endocr J. 2002;49(4):511-6.
[29] Koukourakis MI, Giatromanolaki A, Brekken RA, Sivridis E, Gatter KC, Harris AL, Sage EH. Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Cancer Res. 2003;63(17):5376-80.
[30] Ledda MF, Adris S, Bravo AI, Kairiyama C, Bover L, Chernajovsky Y, Mordoh J, Podhajcer OL. Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of human melanoma cells. Nat Med. 1997;3(2):171-6.
[31] Gilles C, Bassuk JA, Pulyaeva H, Sage EH, Foidart JM, Thompson EW. SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res. 1998;58(23):5529-36.
[32] Porte H, Chastre E, Prevot S, Nordlinger B, Empereur S, Basset P, Chambon P, Gespach C. Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin-3 and BM-40/SPARC genes. Int J Cancer. 1995;64(1):70-5.
[33] Porte H, Triboulet JP, Kotelevets L, Carrat F, Prévot S, Nordlinger B, DiGioia Y, Wurtz A, Comoglio P, Gespach C, Chastre E. Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal carcinoma: implications for prognosis. Clin Cancer Res. 1998;4(6):1375-82.
[34] Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res. 1999;59(17):4453-7.
[35] Schultz C, Lemke N, Ge S, Golembieski WA, Rempel SA. Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo. Cancer Res. 2002;62(21):6270-7.