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Inhibition of ovarian cancer cell metastasis by a fusion polypeptide Tat-ELP

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Abstract

Tumor cell metastasis is a complex, multi-step process that is a major cause of death and morbidity amongst cancer patients. Cell adhesion plays a critical role in the development of metastatic cancer, and it is mediated by interactions between receptors on the cell surface and ligands of the extracellular matrix or other surfaces. Therefore, inhibition of the cell adhesion process appears to be an effective method of preventing metastasis. This work describes a genetically engineered polypeptide with the potential to prevent cell adhesion and inhibit metastasis. We have found that the cell penetrating peptide Tat, fused with elastin-like polypeptide (ELP) inhibited adhesion, spreading, invasion and migration of SKOV-3 ovarian cancer cells in cell culture. Furthermore, we have also confirmed that Tat-ELP has anti-metastatic potential in an experimental ovarian cancer metastasis model in vivo, causing approximately 80% reduction in the tumor burden. Since cell attachment is an important step in tumor cell invasion and metastasis, these results suggest a novel role of Tat-ELP as a therapeutic intervention in cancer metastasis.

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Abbreviations

CPP:

Cell penetrating peptide

ELP:

Elastin-like polypeptide

IP:

Intraperitoneal

RFU:

Relative fluorescence units

PBS:

Phosphate–buffered saline

Tat:

CPP from HIV-1 transcription factor

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Acknowledgments

Grant support: This study was supported by the National Institute of Health R21 CA113813-01A2 and Wendy Will Case Foundation grant. We wish to thank Ms. Rowshan Begum and Ms. Leslie Robinson for technical assistance and critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    Iqbal Massodi, Gene L. Bidwell III, Aisha Davis, Abby Tausend & Drazen Raucher

  2. Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Kimberly Credit & Michael Flessner

Authors
  1. Iqbal Massodi
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  2. Gene L. Bidwell III
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  3. Aisha Davis
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  4. Abby Tausend
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  5. Kimberly Credit
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  7. Drazen Raucher
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Corresponding author

Correspondence to Drazen Raucher.

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Massodi, I., Bidwell, G.L., Davis, A. et al. Inhibition of ovarian cancer cell metastasis by a fusion polypeptide Tat-ELP. Clin Exp Metastasis 26, 251–260 (2009). https://doi.org/10.1007/s10585-009-9237-z

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  • DOI: https://doi.org/10.1007/s10585-009-9237-z

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