Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


Meningiomas are tumours derived from the arachnoid and pia mater. During embryogenesis, these membranes develop from the migrating craniofacial neural crest. We have previously demonstrated that meningiomas have characteristic features of embryonic meninges. Craniofacial neural crest derivatives are affected during normal development and migration by retinoic acid. We speculated, therefore, that meningioma cell migration and invasion would be affected in a similar way. In this study we investigated the mechanisms of invasion and migration in meningiomas and the effects of retinoic acid (RA). We found that low doses of RA inhibit in vitro invasion in meningioma cells, without affecting cell proliferation or viability. The matrix metalloproteinases MMP-2 (72 kDa gelatinase) and MMP-9 (92 kDa gelatinase), which play a key role in invasion in other tumours, are not affected by RA. RA inhibits cell migration on collagen I and fibronectin. A possible mechanism for these effects is provided by the fact that RA strongly stimulates adhesion of meningioma cells to extracellular matrix substrates. As in vitro invasion, migration and decreased adhesion to the extracellular matrix correlate with the clinical manifestation of tumour invasion, we conclude that RA induces a non-invasive phenotype in meningioma cells.


Documento: Artículo
Título:Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion
Autor:Páez Pereda, M.; Hopfner, U.; Pagotto, U.; Renner, U.; Uhl, E.; Arzt, E.; Missale, C.; Stalla, G.K.
Filiación:Max-Planck Institute of Psychiatry, Department of Endocrinology, Kraepelinstr. 10, 80804 Munich, Germany
Department of Neurosurgery, University of Munich, Marchioninistr. 15, 81377 Munich, Germany
Lab. Fisiol./Biol. Molecular, Ciudad Universitaria Pabellon 2, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Dept. of Biomed. Sci./Biotechnology, Div. of Pharmacology, University of Brescia, Via Valsabbina 19, 25124 Brescia, Italy
Palabras clave:Cell adhesion; Meningioma; Retinoic acid; Tumour invasion; collagen type 1; fibronectin; gelatinase a; gelatinase b; matrix metalloproteinase; retinoic acid; article; cancer invasion; cell adhesion; cell proliferation; cell viability; controlled study; embryo development; extracellular matrix; human; human cell; meningioma; neural crest; phenotype; priority journal; Cell Adhesion; Cell Division; Collagenases; Culture Media, Conditioned; Extracellular Matrix; Gelatinases; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Meningeal Neoplasms; Meningioma; Metalloendopeptidases; Neoplasm Invasiveness; Neoplasm Proteins; Tretinoin; Tumor Cells, Cultured
Página de inicio:381
Página de fin:386
Título revista:British Journal of Cancer
Título revista abreviado:Br. J. Cancer
CAS:Collagenases, EC 3.4.24.-; Culture Media, Conditioned; Gelatinases, EC 3.4.24.-; Matrix Metalloproteinase 2, EC; Matrix Metalloproteinase 9, EC; Metalloendopeptidases, EC 3.4.24.-; Neoplasm Proteins; Tretinoin, 302-79-4


  • Akeyson, E.W., McCutcheon, I.F., Management of benign and aggressive intracranial meningiomas (1996) Oncology, 10, pp. 747-759
  • Bertram, J.S., Inhibition of neoplastic transformation in vitro by retinoids (1983) Cencer Surv, 3, pp. 243-262
  • Black, P.M., (1993) Meningiomas Neurosurgery, 32, pp. 643-657
  • Clouthier, D.E., Hosoda, K., Richardson, J.A., Williams, S.C., Yanagisawa, H., Kuwaki, T., Kumada, M., Yanagisawa, Cranial and cardiac neural crest defects in endothelin-A receptor deficient mice (1998) Development, 125, pp. 813-824
  • Durston, A.J., Timmermans, J.P.M., Hage, W.J., Hendriks, H.F.J., Devries, N.J., Heideveld, M., Niewkoop, P.D., Retinoic acid causes an anteroposterior transformation in the developing central nervous system (1989) Nature, 340, pp. 140-144
  • Gale, E., Prince, V., Lumsde, A., Clarke, J., Holder, N., Maden, M., Late effects of retinoic acid on neural crest and aspects of rhombomere (1996) Development, 122, pp. 783-793
  • Harisiadis, L., Miller, R.C., Hall, E.J., Borek, C., A vitamin A analogue inhibits radiation-induced oncogene transformation (1978) Nature, 174, pp. 186-187
  • Helige, C., Smolle, J., Zellnig, G., Hartmann, E., Fink-Puches, R., Kerl, H., Tritthart, H.A., Inhibition of K1735-M2 melanoma cell invasion in vitro by retinoic acid (1993) Clin Exp Metastasis, 2, pp. 409-418
  • Hossein, M.Z., Bertram, J.R., Retinoids, suppress proliferation, induce cell spreading, and up-regulate connexin 43 expression only in postconfluent 10T1/2 cells: Implications, for the role of gap junctional communication (1994) Cell Growth Differ, 5, pp. 1253-1261
  • Hossein, M.Z., Wilkens, L.R., Mehta, P.P., Loewenstein, W., Bertram, J.S., Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation (1089) Carcinogenesis, 10, pp. 1743-1748
  • Jacob, K., Wach, F., Holzapfel, U., Hein, R., Lengyel, E., Buettner, R., Bosserhoff, A.K., In vitro modulation of human melanoma cell invasion and proliferation by all-trans-retinoic acid (1998) Melanoma Res, 8, pp. 211-219
  • Kurihara, Y., Kurihara, H., Suzuki, H., Kodama, T., Maemura, K., Nagai, R., Oda, H., Yazaki, Y., Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-I (1994) Nature, 368, pp. 703-710
  • Ledda, M.F., Adris, S., Bravo, A.I., Kairiyama, C., Bover, L., Chernojovsky, Y., Mordoh, S., Podhajcer, O.L., Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of human melanoma cells (1997) Nat Med, 3, pp. 171-176
  • Lee, Y.M., Osumi-Yamashita, N., Ninomiya, Y., Moon, C.K., Eriksson, U., Eto, K., Retinoic acid stage-dependently alters the migration pattern and identity of hindbrain neural crest cells (1995) Development, 121, pp. 825-837
  • Lotan, R., Retinoids in cancer chemoprevention (1996) FASEB J, 10, pp. 1031-1039
  • McGarvey, T.W., Silberman, S., Persky, B., The effect of butyric acid and retinoic acid on invasion and experimental metastasis of murine melanoma cells (1990) Clin Exp Metastasis, 8, pp. 433-448
  • Mahmood, A., Caccamo, D.V., Tomecek, F.J., Malik, G.M., Atypical and malignant meningiomas: A clinicopathological review (1903) Neurosurgery, 33, pp. 955-963
  • Marshall, H., Nonchev, S., Sham, M.H., Muchamore, I., Lumsden, A., Krumlauf, R., Retinoic acid alters hindbrain hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity (1992) Nature, 360, pp. 737-741
  • Marshall, H., Morrison, A., Studer, M., Pöpperl, H., Krumlauf, R., Retinoids and Hox genes (1996) FASEB J, 10, pp. 969-978
  • Missale, C., Codignola, A., Sigala, S., Finardi, A., Paez-Pereda, M., Sher, E., Spano, P.F., Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines (1998) Proc Natl Acad Sci USA, 95, pp. 5366-5371
  • Moro Balbas, J.A., Gato, A., Alonso Revuelta, M.I., Pastor, J.F., Repressa, J.J., Barbosa, E., Retinoic acid induces changes in the rhomboencephalic neural crest cells migration and extracellular matrix composition in chick embryos (1993) Teratology, 48, pp. 197-206
  • Morris-Kay, G.M., Sokolova, N., Embryonic development and pattern formation (1996) FASEB J, 10, pp. 961-968
  • Murphy, M., Bartlett, P.F., Molecular regulation of neural crest development (1993) Mol Neurobiol, 7, pp. 111-135
  • Nitta, H., Yamashima, T., Yamashita, J., Kubota, T., An ultrastructural and immunohistochemical study of extracellular matrix in meningiomas (1990) Histol Histopathol, 5, pp. 267-274
  • Pagotto, U., Arzberger, T., Hopfner, U., Sauer, J., Renner, U., Newton, C.J., Lange, M., Stalla, G.K., Expression and localisation of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth (1995) J Clin Invest, 96, pp. 2017-2025
  • Palacek, S.P., Loftus, J.C., Ginsberg, M.H., Lauffenburger, D.A., Horwitz, A.F., Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness (1997) Nature, 385, pp. 537-540
  • Rutka, J.T., Myatt, C.A., Giblin, J.R., Davis, R.L., Rosenblum, M.L., Distribution of extracellular matrix proteins in primary human brain tumors: An immunohistochemical analysis (1987) Can J Neurol Sci, 14, pp. 25-30
  • Situ, R., Inman, D.R., Fligiel, S.E., Varani, J., Effects of all-trans-retinoic acid on melanocyte adhesion and motility (1993) Dermatology, 186, pp. 38-44
  • Stetler-Stevenson, W.G., Dynamics of matrix turnover during pathological remodelling of the extracellular matrix (1996) Am J Pathol, 148, pp. 1345-1350
  • Stetler-Stevenson, W.G., Aznavoorian, S., Liotta, L., Tumor cell interactions with the extracellular matrix during invasion and metastasis (1993) Annu Rev Cell Biol, 9, pp. 541-573
  • Toyofuku, T., Yabuki, M., Otsu, K., Kuzuya, T., Hori, M., Tada, M., Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes (1998) J Biol Chem, 273, pp. 12725-12731
  • Woessner J.F., Jr., Matrix metalloproteinases and their inhibitors in connective tissue remodelling (1991) FASEB J, 5, pp. 2145-2154
  • Zülch, K.G., Histological typing of tumors of the central nervous system (1979) International Histologic Classification of Tumors, 21, pp. 47-60. , World Health Organization: Geneva


---------- APA ----------
Páez Pereda, M., Hopfner, U., Pagotto, U., Renner, U., Uhl, E., Arzt, E., Missale, C.,..., Stalla, G.K. (1999) . Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion. British Journal of Cancer, 81(3), 381-386.
---------- CHICAGO ----------
Páez Pereda, M., Hopfner, U., Pagotto, U., Renner, U., Uhl, E., Arzt, E., et al. "Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion" . British Journal of Cancer 81, no. 3 (1999) : 381-386.
---------- MLA ----------
Páez Pereda, M., Hopfner, U., Pagotto, U., Renner, U., Uhl, E., Arzt, E., et al. "Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion" . British Journal of Cancer, vol. 81, no. 3, 1999, pp. 381-386.
---------- VANCOUVER ----------
Páez Pereda, M., Hopfner, U., Pagotto, U., Renner, U., Uhl, E., Arzt, E., et al. Retinoic acid stimulates meningioma cell adhesion to the extracellular matrix and inhibits invasion. Br. J. Cancer. 1999;81(3):381-386.