Abstract
Malignant glioma cells secrete thrombospondin-1 (TSP-1) which participates in the motility of glioma cells, and binds to cell surface αvβ3 and α3β1 integrins, and syndecan-1. This study evaluated the amount of TSP-1 secretion from malignant glioma cells, and the expression of αvβ3 and α3β1 integrins, and syndecan-1. The amounts of TSP-1 in the supernatants from 10 malignant glioma cell lines and eight non-glioma malignant tumor cell lines were measured by enzyme-linked immunosorbent assay. Expression of αvβ3 and α3β1 integrins, and syndecan-1 were examined by flow cytometry. The amounts of TSP-1 secreted by malignant glioma cells were 43 to 2431 ng/1 × 106 cells/24 h (mean ± SD=626 ± 792). Seven of 10 glioma cell lines secreted more than 100 ng of TSP-1 and three of these cell lines secreted more than 1 μg. Seven of eight non-glioma cell lines secreted less than 100 0ng of TSP-1. All glioma cell lines expressed α3β1 integrin and syndecan-1, and seven of 10 glioma cell lines expressed αvβ3 integrin. Treatment of the glioma cell lines with TGF-β2 did not change the expression of αvβ3 integrin. These results suggest that malignant glioma cells secrete high levels of TSP-1, which may be important in the migration of glioma cells via interactions with αvβ3 and α3β1 integrins, and syndecan-1.
Similar content being viewed by others
References
DD Roberts (1996) ArticleTitleRegulation of tumor growth and metastasis by thrombospondin 1 FASEB J 10 1183–1191
GP Tuszynski RF Nicosia (1996) ArticleTitleThe role of thrombospondin-1 in tumor progression and angiogenesis Bioessays 18 71–76
P Bornstein EH Sage (1994) ArticleTitleThrombospondins Methods Enzymol 245 62–85
JM Sipes HC Krutzsch J Lawler DD Roberts (1999) ArticleTitleCooperation between thrombospondin-1 type 1 repeat peptides and αvβ3 integrin ligands to promote melanoma cell spreading and focal adhesion kinase phosphorylation J Biol Chem 274 22755–22762
N Guo NS Templeton H Al-Barazi JA Cashel JM Sipes HC Krutzsch DD Roberts (2000) ArticleTitleThrombospondin-1 promotes α3β1 integrin-mediated adhesion and neurite-like outgrowth and inhibits proliferation of small cell lung carcinoma cells Cancer Res 60 457–466
HC Krutzsch HC Krutzsch BJ Choe JM Sipes N Guo DD Roberts (1999) ArticleTitleIdentification of an α3β1 integrin recognition␣sequence in thrombospondin-1 J Biol Chem 274 24080–24086
DJ Carey (1997) ArticleTitleSyndecans: multifunctional cell-surface co-receptors Biochem J 327 1–16
Z Wang JM Symons SL Goldstein A McDonald JH Miner JA Kreidberg (1999) ArticleTitleα3β1 integrin regulates epithelial cytoskeletal organization J Cell Sci 112 2925–2935
W Paulus I Baur D Schuppan W Roggendorf (1993) ArticleTitleCharacterization of integrin receptors in normal and neoplastic human brain Am J Pathol 143 154–163
BB Tysnes LF Larsen GO Ness R Mahesparan K Edvardsen I Garcia-Cabrera R Bjerkvig (1996) ArticleTitleStimulation of glioma-cell migration by laminin and inhibition by anti-α3 and anti-β1 integrin antibodies Int J Cancer 67 777–784
L Bello M Francolini P Marthyn J Zhang RS Carroll DC Nikas JF Strasser R Villani DA Cheresh PM Black (2001) ArticleTitleαvβ3 and αvβ5 integrin expression in glioma periphery Neurosurgery 49 380–390
CL Gladson DA Cheresh (1991) ArticleTitleGlioblastoma expression of vitronectin and the αvβ3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest 88 1924–1932
T Kawataki H Naganuma A Sasaki H Yoshikawa K Tasaka H Nukui (2000) ArticleTitleCorrelation of thrombospondin-1 and transforming growth factor-β expression with malignancy of glioma Neuropathology 20 161–169
A Sasaki H Naganuma E Satoh T Kawataki K Amagasaki H Nukui (2001) ArticleTitleParticipation of thrombospondin-1 in the activation of latent transforming growth factor-β in malignant glioma cells Neurol Med Chir (Tokyo) 41 253–259
K Amagasaki A Sasaki G Kato S Maeda H Nukui H Naganuma (2001) ArticleTitleAntisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cells Int J Cancer 94 508–512
M Platten W Wick C Wild-Bode S Aulwurm J Dichgans M Weller (2000) ArticleTitleTransforming growth factors β1 (TGF-β1) and TGF-β2 promote glioma cell migration via up-regulation of αvβ3 integrin expression Biochem Biophys Res Commun 268 607–611
H Naganuma A Sasaki E Satoh T Sakihama K Tasaka H Nukui (1994) ArticleTitleImproved bioassay for the detection of transforming growth factor-β1 and β2 in malignant gliomas Neurol Med Chir (Tokyo) 34 143–149
A Sasaki H Naganuma E Satoh M Nagasaka S Isoe S Nakano H Nukui (1995) ArticleTitleSecretion of transforming growth factor-β1 and -β2 by malignant glioma cells Neurol Med Chir (Tokyo) 35 423–430
JC Adams N Kureishy AL Taylor (2001) ArticleTitleA role for syndecan-1 in coupling fascin spike formation by thrombospondin-1 J Cell Biol 152 1169–1182
RO Hynes (1987) ArticleTitleIntegrins: a family of cell surface receptors Cell 48 549–554
E Ruoslahti MD Pierschbacher (1987) ArticleTitleNew perspectives in cell adhesion: RGD and integrins Science 238 491–497
JW Smith DA Cheresh (1990) ArticleTitleIntegrin αvβ3-ligand interaction. Identification of a heterodimeric RGD binding site on the vitronectin receptor. J Biol Chem 265 2168–2172
S Chatterjee A Matsumura J Schradermeier GY Gillespie (2000) ArticleTitleHuman malignant glioma therapy using anti-αvβ3 integrin agents J Neurooncol 46 135–144
T Taga A Suzuki I Gonzalez-Gomez FH Gilles M Stins H Shimada L Barsky KI Weinberg WE Laug (2002) ArticleTitleαv-integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin Int J Cancer 98 690–697
L Bello V Lucini C Giussani G Carrabba M Pluderi F Scaglione G Tomei R Villani PM Black A Bikfalvi RS Carroll (2003) ArticleTitleIS20I, a specific αvβ3 integrin inhibitor, reduces glioma growth in vivo Neurosurgery 52 177–186
S Isoe H Naganuma S Nakano A Sasaki E Satoh M Nagasaka S Maeda H Nukui (1998) ArticleTitleResistance to growth inhibition by transforming growth factor-β in malignant glioma cells with functional receptors J Neurosurg 88 529–534
EI Deryugina MA Bourdon (1996) ArticleTitleTenascin mediates human glioma cell migration and modulates cell migration on fibronectin J Cell Sci 109 643–652
MA Bourdon E Ruoslahti (1989) ArticleTitleTenascin mediates cell attachment through an RGD-dependent receptor J Cell Biol 108 1149–1155
V Pijuan-Thompson JR Grammer J Stewart RL Silverstein SF Pearce GP Tuszynski JE Murphy-Ullrich CL Gladson (1999) ArticleTitleRetinoic acid alters the mechanism of attachment of malignant astrocytoma and neuroblastoma cells to thrombospondin-1 Exp Cell Res 25 86–101
S Schultz-Cherry J Lawler JE Murphy-Ullrich (1994) ArticleTitleThe type 1 repeats of thrombospondin 1 activate latent transforming growth factor-β J Biol Chem 269 26783–26788
JH Kehrl LM Wakefield AB Roberts S Jakowlew M Alvarez-Mon R Derynck MB Sporn AS Fauci (1986) ArticleTitleProduction of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth J Exp Med 163 1037–1050
GE Ranges IS Figari T Espevik MA Palladino SuffixJr (1987) ArticleTitleInhibition of cytotoxic T cell development by transforming growth factor β and reversal by recombinant tumor necrosis factor α J Exp Med 166 991–998
T Espevik IS Figari MR Shalaby GA Lackides GD Lewis HM Shepard MA Palladino SuffixJr (1987) ArticleTitleInhibition of cytokine production by cyclosporin A and transforming growth factor β J Exp Med 166 571–576
H Naganuma A Sasaki E Satoh M Nagasaka S Nakano S Isoe K Tasaka H Nukui (1994) ArticleTitleInhibition of tumor necrosis factor-α and -β secretion by lymphokine activated killer cells by transforming growth factor-β Jpn J Cancer Res 85 952–957
H Naganuma A Sasaki E Satoh M Nagasaka S Nakano S Isoe K Tasaka H Nukui (1996) ArticleTitleTransforming growth factor-β inhibits interferon-γ secretion by lymphokine-activated killer cells stimulated with tumor cells Neurol Med Chir (Tokyo) 36 789–795
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Naganuma, H., Satoh, E., Asahara, T. et al. Quantification of thrombospondin-1 secretion and expression of αvβ3 and α3β1 integrins and syndecan-1 as cell-surface receptors for thrombospondin-1 in malignant glioma cells. J Neurooncol 70, 309–317 (2004). https://doi.org/10.1007/s11060-004-9167-1
Issue Date:
DOI: https://doi.org/10.1007/s11060-004-9167-1