gms | German Medical Science

127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

Genetic profiling of brain- and bone-seeking clones of MDA-MB-231 breast cancer cells

Meeting Abstract

  • Andreas Stark - UKSH Campus Kiel, Neurochirurgie, Kiel, Deutschland
  • Rolf Mentlein - UKSH Campus Kiel, Neurochirurgie, Kiel, Deutschland
  • H. Maximilian Mehdorn - UKSH Campus Kiel, Neurochirurgie, Kiel, Deutschland
  • Janka Held-Feindt - UKSH Campus Kiel, Neurochirurgie, Kiel, Deutschland

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch083

DOI: 10.3205/10dgch083, URN: urn:nbn:de:0183-10dgch0834

Veröffentlicht: 17. Mai 2010

© 2010 Stark 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

Introduction: Metastasis to the brain and bone is a major source of morbidity and mortality in cancer patients. We report genetic profiling of brain- and bone-selective invasive and metastatic MDA-MB-231 breast cancer cells using cDNA Array technology and real-time RT-PCR.

Materials and methods: Gene profiling was performed using the 16K gene chip of the National Human Genome Research Institute, NIH, USA. Results were verified by quantative real-time RT-PCR. Protein expression was examined using enzyme-linked immunosorbent assays (ELISA) and western blotting. Migration and invasion assays were performed with the QCM 96-well Migration/Invasion Assay +/- specific MMP inhibitors.

Results: cDNA array analysis revealed significant over- or underexpression in brain- and/or bone-seeking cells of 113 genes. 9 gene sequences were chosen for data validation using real-time RT-PCR. Herein, significant changes in both selective clones were found for: (1) matrix-metallo-proteinase 1 (MMP-1), (3) the metastasis suppressor gene KISS-1 and (2) vascular factors endoglin and TIE-1. These genes were chosen for further analysis. Functional experiments determined the potential role for breast cancer metastasis to the brain and bone. In vitro experiments were supplemented by examinations on human tumor tissue. Herein, (1) the expression of MMP-1 and MMP-9 was increased in brain-metastatic cells (mRNA and -protein level). (2) We found significantly decreased expression of metastases suppressor genes in human breast cancer brain metastases: KISS-1, BRMS-1, MKK4, KAI-1 and Maspin (SERPINB5).

Conclusion: (1) MMP-1 and -9 were overexpressed in brain-seeking 231-clones. MMP-1 and -9 inhibitors lead to decreased invasive and migratory potential in vitro. (2) Several metastasis-suppressor genes, including Maspin (SERPIN B5) were decreased in human breast cancer brain metastases.