Induction of glioma cell migration by vitronectin in human serum and cerebrospinal fluid

Yuji Fukushima M.D., Ph.D.1,2, Masakazu Tamura M.D., Ph.D.3, Hidemitsu Nakagawa M.D., Ph.D.3, and Kazuyuki Itoh M.D., Ph.D.1
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  • 1 Departments of Biology and
  • | 3 Neurosurgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka; and
  • | 2 Department of Neurosurgery, Osaka Rosai Hospital, Sakai, Japan
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Object

Malignant gliomas are often highly invasive and can migrate along blood vessels. The purpose of the current study was to identify the substance in human serum and/or cerebrospinal fluid (CSF) that promotes glioma cell migration.

Methods

The authors used a Boyden chamber cell migration assay to study the effect of serum from patients with glioma and healthy volunteers on chemotaxis of A172 human glioma cells. Heat inactivation, trypsinization, and ultra-filtration of serum were used to establish the nature of the active factor. Vitronectin and fibronectin were chosen for further investigations; chemotactic effects were studied in both serum and CSF.

Results

Serum from both patients with glioma and healthy volunteers was found to promote chemotaxis of human glioma cells. This activity was greatly reduced by heat inactivation or trypsinization. Fractionation of the serum by ultrafiltration through membranes with various pore sizes showed that the active molecule was larger than 50 kD. Antibodies against integrin αv or αvβ5 or arginine-glycine-aspartic acid–containing peptides, both of which block the vitronectin–glioma cell interactions, significantly reduced serum-induced cell migration, whereas blocking the interaction of glioma cells with fibronectin had no effect. Furthermore, the ability of serum to promote the migration of A172 or T98G glioma cells was suppressed by immunodepletion of vitronectin and restored by the addition of exogenous vitronectin. The migration of glioma cells induced by CSF collected from the postoperative cavity of a malignant glioma patient was also reduced by blocking the interaction of glioma cells with vitronectin.

Conclusions

These results suggest that vitronectin is one of the major factors in serum- and CSF-induced glioma cell migration.

Abbreviations used in this paper:

CSF = cerebrospinal fluid; DMEM = Dulbecco modified Eagle medium; GBM = glioblastoma multiforme; GRGDSP = glycine-arginine-glycine-aspartic acid-serine-proline; GRGESP = glycine-arginine-glycine-glutamic acid-serine-proline; IgG = immunoglobulin G; RGD = arginine-glycine-as-partic acid; RGE = arginine-glycine-glutamic acid.

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  • 1

    Bello L, , Giussani C, , Carrabba G, , Pluderi M, , Costa F, & Bikfalvi A: Angiogenesis and invasion in gliomas. Cancer Treat Res 117:263284, 2004

    • Search Google Scholar
    • Export Citation
  • 2

    Bolteus AJ, , Berens ME, & Pilkington GJ: Migration and invasion in brain neoplasms. Curr Neurol Neurosci Rep 1:225232, 2001

  • 3

    Chatterjee S, , Matsumura A, , Schradermeier J, & Gillespie GY: Human malignant glioma therapy using anti-alpha(v)beta3 integrin agents. J Neurooncol 46:135144, 2000

    • Search Google Scholar
    • Export Citation
  • 4

    Chicoine MR, , Madsen CL, & Silvergeld DL: Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb, NGF, and TNFα. Neurosurgery 36:11651171, 1995

    • Search Google Scholar
    • Export Citation
  • 5

    Chicoine MR, & Silvergeld DL: Mitogens as motogens. J Neurooncol 35:249257, 1997

  • 6

    Chintala SK, , Sawaya R, , Gokaslan ZL, , Fuller G, & Rao JS: Immunohistochemical localization of extracellular matrix proteins in human glioma, both in vivo and in vitro. Cancer Lett 101:107114, 1996

    • Search Google Scholar
    • Export Citation
  • 7

    Ding Q, , Stewart J Jr, , Prince CW, , Chang PL, , Trikha M, & Han X, et al.: Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Cancer Res 62:53365343, 2002

    • Search Google Scholar
    • Export Citation
  • 8

    Fukushima Y, , Ohnishi T, , Arita N, , Hayakawa T, & Sekiguchi K: Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells. Int J Cancer 76:6372, 1998

    • Search Google Scholar
    • Export Citation
  • 9

    Giese A, , Bjerkvig R, , Berens ME, & Westphal M: Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21:16241636, 2003

    • Search Google Scholar
    • Export Citation
  • 10

    Giese A, & Westphal M: Glioma invasion in the central nervous system. Neurosurgery 39:235252, 1996

  • 11

    Gladson CL: The extracellular matrix of gliomas: modulation of cell function. J Neuropathol Exp Neurol 58:10291040, 1999

  • 12

    Gladson CL, & Cheresh DA: Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest 88:19241932, 1991

    • Search Google Scholar
    • Export Citation
  • 13

    Gladson CL, , Wilcox JN, , Sanders L, , Gillespie GY, & Cheresh DA: Cerebral microenvironment influences expression of the vitronectin gene in astrocytic tumors. J Cell Sci 108:947956, 1995

    • Search Google Scholar
    • Export Citation
  • 14

    Gunther W, , Skaftnesmo KO, , Arnold H, & Terzis AJ: Molecular approaches to brain tumour invasion. Acta Neurochir (Wien) 145:10291036, 2003

    • Search Google Scholar
    • Export Citation
  • 15

    Hamel W, & Westphal M: Growth factors in gliomas revisited. Acta Neurochir (Wien) 142:113138, 2000

  • 16

    Hedberg KK, , Stauff C, , Hoyer-Hansen G, , Ronne E, & Griffith OH: High-molecular-weight serum protein complexes differentially promote cell migration and the focal adhesion localization of the urokinase receptor in human glioma cells. Exp Cell Res 257:6781, 2000

    • Search Google Scholar
    • Export Citation
  • 17

    Lopes MB: Angiogenesis in brain tumors. Microsc Res Tech 60:225230, 2003

  • 18

    Mahesparan R, , Read TA, , Lund-Johansen M, , Skaftnesmo KO, , Bjerkvig R, & Engebraaten O: Expression of extracellular matrix components in a highly infiltrative in vivo glioma model. Acta Neuropathol (Berl) 105:4957, 2003

    • Search Google Scholar
    • Export Citation
  • 19

    Mahesparan R, , Tysnes BB, , Edvardsen K, , Haugeland HK, , Cabrera IG, & Lund-Johansen M, et al.: Role of high molecular weight extra-cellular matrix proteins in glioma cell migration. Neuropathol Appl Neurobiol 23:102112, 1997

    • Search Google Scholar
    • Export Citation
  • 20

    Manning TJ Jr, , Parker JC, & Sontheimer H: Role of lysophosphatidic acid and rho in glioma cell motility. Cell Motil Cytoskeleton 45:185199, 2000

    • Search Google Scholar
    • Export Citation
  • 21

    Oz B, , Karayel FA, , Gazio NL, , Ozlen F, & Balci K: The distribution of extracellular matrix proteins and CD44S expression in human astrocytomas. Pathol Oncol Res 6:118124, 2000

    • Search Google Scholar
    • Export Citation
  • 22

    Paulus W, , Baur I, , Schuppan D, & Roggendorf W: Characterization of integrin receptors in normal and neoplastic human brain. Am J Pathol 143:154163, 1993

    • Search Google Scholar
    • Export Citation
  • 23

    Preissner KT: Structure and biological role of vitronectin. Annu Rev Cell Biol 7:275310, 1991

  • 24

    Rao JS: Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 3:489501, 2003

  • 25

    Rascher G, , Fischmann A, , Kroger S, , Duffner F, , Grote EH, & Wolburg H: Extracellular matrix and the blood-brain-barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin. Acta Neuropathol 104:8591, 2002

    • Search Google Scholar
    • Export Citation
  • 26

    Rutka JT, , Myatt CA, , Giblin JR, , Davis RL, & Rosenblum ML: Distribution of extracellular matrix proteins in primary human brain tumors: an immunohistochemical analysis. Can J Neurol Sci 14:2530, 1987

    • Search Google Scholar
    • Export Citation
  • 27

    Sawaya R, , Cummins CJ, , Smith BH, & Kornblith PL: Plasma fibronectin in patients with brain tumors. Neurosurgery 16:161165, 1985

  • 28

    Steiner MR, , Urso JR, , Klein J, & Steiner SM: Multiple astrocyte responses to lysophosphatidic acids. Biochim Biophys Acta 1582:154160, 2002

    • Search Google Scholar
    • Export Citation
  • 29

    Suzuki S, , Oldberg A, , Hayman EG, , Pierschbacher MD, & Ruoslahti E: Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin. Embo J 4:25192524, 1985

    • Search Google Scholar
    • Export Citation
  • 30

    Taga T, , Suzuki A, , Gonzalez-Gomez I, , Gilles FH, , Stins M, & Shimada H, et al.: alpha v-Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin. Int J Cancer 98:690697, 2002

    • Search Google Scholar
    • Export Citation
  • 31

    Thorsen F, & Tysnes BB: Brain tumor cell invasion, anatomical and biological considerations. Anticancer Res 17:41214126, 1997

  • 32

    Tonn JC, & Goldbrunner R: Mechanisms of glioma cell invasion. Acta Neurochir Suppl 88:163167, 2003

  • 33

    Tysnes BB, & Mahesparan R: Biological mechanisms of glioma invasion and potential therapeutic targets. J Neurooncol 53:129147, 2001

  • 34

    Yoshioka K, , Matsumura F, , Akedo H, & Itoh K: Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. J Biol Chem 273:51465154, 1998

    • Search Google Scholar
    • Export Citation
  • 35

    Zhou Y, , Larsen PH, , Hao C, & Yong VW: CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem 277:4948149487, 2002

    • Search Google Scholar
    • Export Citation

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