Fragments of SLIT3 inhibit cellular migration

Schubert,Thomas; Denk,Alexandra  E.; Ruedel,Anke; Kaufmann,Simone; Hustert,Elisabeth; Bastone,Patrizia; Bosserhoff,Anja  K.

doi:10.3892/ijmm.2012.1098

November 2012 Volume 30 Issue 5

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November 2012 Volume 30 Issue 5

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Article

Fragments of SLIT3 inhibit cellular migration

Authors:
- Thomas Schubert
- Alexandra E. Denk
- Anke Ruedel
- Simone Kaufmann
- Elisabeth Hustert
- Patrizia Bastone
- Anja K. Bosserhoff
View Affiliations / Copyright

Affiliations: Institute of Pathology, University of Regensburg, Regensburg, Germany, Scil Technology GmbH, Martinsried, Germany
Pages: 1133-1137
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Published online on: August 20, 2012

https://doi.org/10.3892/ijmm.2012.1098
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Abstract

The repellent factor family of Slit molecules has been described as having a repulsive function in the developing nervous system on growing axons expressing the Roundabout (Robo) receptors. Recent studies determined the effects of Slit molecules on the migratory and invasive potential of several types of tumor cells but also on synovial fibroblasts (SFs) derived from rheumatoid arthritis (RA) patients. To optimize a potential therapeutic application we aimed at generatingfragments of Slit3 showing the same functional ability as the full-length molecule but having the advantage of a smaller size. Recombinant Slit3 proteins were expressed and analyzed by western blotting. Their activity was defined by functional assays such as migration assays with RASF and melanoma cells. Recombinant Slit3 containing only leucine rich repeat domain 2 (D2), the domain important for Robo binding and the minimal functional unit D2 dNC were both able to inhibit migration of RASFs as effectively as Slit3 with all 4 repeats. Collectively, our data showed that the ability of Slit3 to reduce the migratory activity of synovial cells from patients with RA and melanoma cells can be mimicked by small protein fragments derived from Slit3. Slit3 fragments may be helpful in therapeutic attempts; however, further studies are necessary in order to elucidate their activity in vivo.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Fragments of SLIT3 inhibit cellular migration

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