gms | German Medical Science

65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

11. - 14. Mai 2014, Dresden

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Expression of ADAM8 mediates brain metastasis of breast cancer cells

Meeting Abstract

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  • Catharina Conrad - Klinik für Neurochirurgie, Philipps-Universität Marburg, Marburg
  • Uwe Schlomann - Klinik für Neurochirurgie, Philipps-Universität Marburg, Marburg
  • Mathilde Romagnoli - Department of Biochemistry, Tufts Medical School, Boston, USA
  • Nora D. Mineva - Department of Biochemistry, Tufts Medical School, Boston, USA
  • Gail E. Sonenshein - Department of Biochemistry, Tufts Medical School, Boston, USA
  • Peter Anderson - King’s College London, Blood Brain Barrier Group, London, UK
  • Jane Preston - King’s College London, Blood Brain Barrier Group, London, UK
  • Jessica Prüssmeyer - Pharmakologie, RWTH Aachen, Aachen
  • Andreas Ludwig - Pharmakologie, RWTH Aachen, Aachen
  • Christopher Nimsky - Klinik für Neurochirurgie, Philipps-Universität Marburg, Marburg
  • Jörg W. Bartsch - Klinik für Neurochirurgie, Philipps-Universität Marburg, Marburg

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocP 061

doi: 10.3205/14dgnc457, urn:nbn:de:0183-14dgnc4579

Veröffentlicht: 13. Mai 2014

© 2014 Conrad et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

Objective: Brain metastases outnumber primary neoplasms ten-fold, and are associated with a poor prognosis. Patients with metastatic, triple negative breast cancers are at high risk (25-46%) of developing brain metastases at some point in the course of their disease. We evaluated the role of ADAM8, a metalloprotease-disintegrin, in facilitating trans-endothelial migration and its potential functional role in the formation of brain metastases.

Method: Stable ADAM8 knock-down clones of the breast cancer cell line MB-231 (shA8) were subjected to functional assays including migration, sphere formation and transmigration through a Blood Brain Barrier model consisting of endothelial cells and astrocytes. In addition, MMP expression was analysed in MB-231 control and shA8 cells by qPCR. Furthermore, comparative phospho-kinase arrays were utilized. The cell model data was correlated to brain metastases from primary breast tumors.

Results: It was noted that increased ADAM8 expression was found in 34% of primary site tumors, this was found to be 2-fold higher in brain metastases. In transendothelial migration assays, MB-231 knock-down cells showed a reduced endothelial adhesion as well as a reduced transmigratory capacity both in serum-induced transmigration and in transmigration triggered by the chemokine SDF-1, a mediator of metastasis. This was further supported by the blood-brain barrier in vitro model as well as Matrigel invasion assays. ADAM8 knockdown leads to reduced ERK1/2 and CREB phosphorylation and furthermore affected the expression levels of MMP-9.

Conclusions: Our results suggest that ADAM8 is an important mediator for brain metastasis of breast cancer by affecting transendothelial migration and may offer an attractive target for therapeutic intervention.