gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Differential expression and function of Matrix Metalloproteinases in brain- and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells

Expression und funktionelle Bedeutung von Matrix-Metalloproteinasen in hirn- und knochenselektiven MDA-MB-231-Zellen

Meeting Abstract

  • corresponding author A.M. Stark - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • B. Anuszkiewicz - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • R. Mentlein - Institut für Anatomie, Christian-Albrechts-Universität zu Kiel
  • H.M. Mehdorn - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • J. Held-Feindt - Klinik für Neurochirurgie im Universitätsklinikum Schleswig-Holstein, Campus Kiel

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 06.86

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Stark et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Matrix-Metalloproteinases (MMPs) play a crucial role in migration, invasion and metastasis of breast cancer. We examined the mRNA and protein expression of several MMPs in recently established brain- and bone-seeking clones of MDA-MB-231 breast cancer cells. In addition, we examined their transcriptional regulation and their functional role in the metastatic process.

Methods: MMP mRNA expression was examined using real-time reverse transcription polymerase chain reaction. Protein expression was examined using enzyme linked immunosorbent essay (ELISA). The inducibility of mRNA and protein expression was tested with different growth factors and cytokines (TPA (phorbol 12-myristate 13-acetate; 50µM); epidermal growth factor, transforming growth factor β (20ng/ml both)). Migration and invasion assays were performed with the QCMTM 96-Well Migration / Invasion Assay (8µm; Chemicon) over 24h with or without specific MMPs inhibitors (MMP Inhibitor I Mix (5µM); MMP-2/MMP-9 Inhibitor III (50µM); EMD Biosciences).

Results: We found significantly higher mRNA-expression of MMP-1 and -9 in brain-seeking 231-clones in comparison to 231-bone and -parental cells. In contrast, the mRNA expression of MMP-3 and -14 was comparable while the expression of MMP-13 was lower in differential metastatic cells. MMP-2 and -8 were not expressed in 231-cells. Using ELISA, the amount of total as well as the amount of active MMP-1 and -9 was also higher in brain-seeking cells. TPA stimulation experiments revealed that MMP-1 and -9-transcription was inducible on the mRNA and protein level in 231-parental but not in 231-brain or -bone. 231-brain shows the highest migration and invasive capacity which could be decreased by the application of MMP-1 and/or MMP-9 inhibitor.

Conclusions: Our results indicate functional importance of MMP-1 and -9 overexpression in brain selective metastatic breast cancer cells.