Abstract
Annexin II is a calcium and phospholipid binding protein and a substrate for protein-tyrosine kinases. Increased levels of annexin II are observed in various cancer cells and tissues, and the molecule has been proposed as a marker of malignancy in vivo. Annexin II was expressed in four glioma cell lines (D-54MG, D-37MG, U251MG and GaMG), as determined by Western blot analyses, immunofluorescence staining and flow cytometric measurements. In addition, annexin II expression was also found in cryostat sections obtained from 15 consecutive brain tumor biopsies: Ten were histologically classified as glioblastomas, one as an astrocytoma, two as meningiomas and two as brain metastases. Cultured spheroids from the glioma cell lines and from three of the glioblastoma biopsies showed lower levels of annexin II, than found in the monolayers of the cell lines and in the freshly cut biopsies. The annexin II expression of the cell lines were not found to be related to their proliferative, migratory or invasive properties. These findings indicate that although annexin II may serve as a marker of malignancy in vivo, its expression can be reduced in vitro, and appear unrelated to malignant features of glioma cell lines.
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Petersdorf SH, Livingston RB: High dose chemotherapy for the treatment of malignant brain tumors. J Neurooncol 20: 155–163, 1994
Bigner SH, Johnston WW: Cytopathology of the nervous system. E Arnold, Chapter 9: 161–174, 1994
Torp SH, Helseth E, Dalen A, Unsgaard G: Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas. Acta Neurochir Wien 117: 182–186, 1992
McKeever PE, Davenport RD, Shakui P: Patterns of antigenic expression of human glioma cells. Crit Rev Neurobiol 6: 119–147, 1991
Giordana MT, Migheli A, Mocellini C, Villare F, Schiffer D: Immunohistochemical observations on rat radial glia: relationship with the origin of ethylnitrosurea-induced tumors. Acta Neuropathol Berl 84: 387–393, 1992
Bilzer T, Stavrou D, Wechsler W, Wohler B, Keiditsch E: Antigen variation in a human glioblastoma: from the primary tumor to the second recurrence, permanent cell line and xenotransplantation tumors. Anticancer Res 11: 547–553, 1991
Paulus W, Huettner C, Tonn JC: Collagens, integrins and the mesenchymal drift in glioblastomas: a comparison of biopsy specimens, spheroid and early monolayer cultures. Int J Cancer 58: 841–846, 1994
Roseman BJ, Bollen A, Hsu J, Lamborn K, Israel MA: Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 6: 561–567, 1994
Reeves SA, Chavez-Kappel C, Davis R, Rosenblum M, Israel MA: Developmental regulation of annexin II (lipocortin 2) in human brain and expression in high grade glioma. Cancer Res 52: 6871–6876, 1992
McLeod JD, Goodall A, Jelic P, Bolton C: Changes in the cellular distribution of lipocortin-I (Annexin-I) in C6 glioma cells after exposure to dexamethasone. Biochem Pharmacol 50: 1103–1107, 1995
Giambanco I, Sorci G, Antonioli S, Rambotti MG, Spreca A, Bocchini V, Donato R: Immunocytochemical analyses of annexin V (CaBP33) in a human-derived glioma cell line. Expression of annexin V depends on cellular growth state. FEBS Lett 323: 45–50, 1993
Tressler RJ, Updyke TV, Yeatman T, Nicolson GL: Extracellular annexin II is associated with divalent cation-dependent tumor cell-endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. J Cell Biochem 53: 265–276, 1993
Engebraaten O, Bjerkvig R, Lund-Johansen M, Wester K, Pedersen PH, Mörk S, Backlund EO, Laerum OD: Interaction between human brain tumour biopsies and fetal rat brain tissue in vitro. Acta Neuropathol Berl 81: 130–140, 1990
Kristoffersen EK, Ulvestad E, Björge L, Aarli Å, Matre R: Fc-gamma-receptor activity of placental annexin II. Scand J Immunol 40: 237–242, 1994
Akslen LA, Andersen KJ, Bjerkvig R: Characteristics of human and rat glioma cells grown in a defined medium. Anticancer Res 8: 797–803, 1988
Bigner DD, Bigner SH, Pontén J, Westermark B, Mahaley MS, Ruoslahti E, Herschman H, Eng LF, Wikstrand CJ: Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 40: 201–229, 1981
Bjerkvig R: Spheroid Culture in Cancer Research. CRCPress, Boca Raton, Florida 1992
Engebraaten O, Bjerkvig R, Pedersen P-H, Laerum OD: Effects of EGF, bFGF, NGF and PDGF (BB) on cell migratory and invasive capacities of human brain-tumour biopsies in vitro. Int J Cancer 53: 209–214, 1993
Bjerkvig R, Laerum OD, Mella O: Glioma cell interactions with fetal rat brain aggregates in vitro, and with brain tissue in vivo. Cancer Res 46: 4071–4079, 1986
Laemmli UK: Cleavage of structural proteins during the assembly of the bacteriophage T4. Nature 227: 680–685, 1970
Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76: 4350–4354, 1979
de la Monte SM, Bhavani K, Xu YY, Puisieux A, Wands JR: Modulation of p36 gene-expression in human neuronal cells. J Neurol Sci 128: 122–133, 1995
Perretti M, Flower RJ: Measurement of lipocortin 1levels in murine peripheral blood leukocytes by flow cytometry: modulation by glucocorticoids and inflammation. Br J Pharmacol 118: 605–610, 1996
McLeod JD, Bolton C: Dexamethasone induces an increase in intracellular and membrane-associated lipocortin-1 (annexin 1) in rat astrocyte primary cultures. Cell Mol Neurobiol 15: 193–205, 1995
Batouri HE, Claisse D, Bellon G, Antonicelli F, Haye B: In vivo modulation of annexins I, II and V expression by thyroxine and methylthiouracil. Eur J Biochem 242: 506–511, 1996
Lund-Johansen M, Engebraaten O, Bjerkvig R, Laerum OD: Invasive glioma cells in tissue culture. Anticancer Res 10: 1135–1152, 1990
Raynal P, Pollard HB: Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium-and phospholipid-binding proteins. Biochim Biophys Acta 1197: 63–93, 1994
Baltuch GH, Dooley NP, Villemure JG, Yong VW: Protein kinase C and growth regulation of malignant gliomas. Can J Neurol Sci 22: 264–271, 1995
Couldwell WT, Antel JP, Apuzzo ML, Yong VW: Inhibition of growth of established human glioma cell lines by modulators of the protein kinase C system. J Neurosurg 73: 594–600, 1990
Tysnes O-B, Laerum OD: Differential effects of 12-0-tetradecanoyl-13-phorbol acetate (TPA) on growth, migration and invasion of a human glioma cell line. Anticancer Res 13: 1325–1330, 1993
Creutz CE: The annexins and exocytosis. Science 258: 924–931, 1992
Gerke V, Weber K: Calcium-dependent conformational changes in the 36-kDa subunit of intestinal protein I related to the cellular 36-kDa target of Rous sarcoma virus tyrosine kinase. J Biol Chem 260: 1688–1695, 1985
Chung CY, Erickson HP: Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C.J Cell Biol 126: 539–548, 1994
Prieto AL, Edelman GM, Crossin KL: Multiple integrins mediate cell attachment to cytoactin/tenascin. Proc Natl Acad Sci USA 90: 10154–10158, 1993
Berendes R, Burger A, Voges D, Demange P, Huber R: Calcium influx through annexin V ion channels into large unilamellar vesicles measured with fura-2. FEBS Lett 317: 131–134, 1993
Nygaard SJT, Laerum OD, Tysnes O-B: Heterogeneous effects of bradykinin and A23187 on glioma growth, migration and invasion. Int J Oncol 5: 69–75, 1994
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Nygaard, S., Haugland, H., Kristoffersen, E. et al. Expression of annexin II in glioma cell lines and in brain tumor biopsies. J Neurooncol 38, 11–18 (1998). https://doi.org/10.1023/A:1005953000523
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DOI: https://doi.org/10.1023/A:1005953000523