Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation

  • Authors:
    • Johanna E. Welch
    • Per Bengtson
    • Katrin Svensson
    • Anders Wittrup
    • Guido J. Jenniskens
    • Gerdy B. Ten Dam
    • Toin H. Van Kuppevelt
    • Mattias Belting
  • View Affiliations

  • Published online on: April 1, 2008     https://doi.org/10.3892/ijo.32.4.749
  • Pages: 749-756
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Abstract

The growth-promoting polyamines are polybasic compounds that efficiently enter cancer cells by as yet incompletely defined mechanisms. Strategies to inhibit their internalization may have important implications in the management of tumor disease. Here, we show that cellular binding and uptake of polyamines are inhibited by a single chain variable fragment anti-heparan sulfate (HS) antibody. Polyamine uptake was inhibited in a dose-dependent manner, and was associated with compensatory up-regulation of ornithine decarboxylase (ODC), i.e. the key enzyme of the polyamine biosynthesis pathway. Conversely, depletion of intracellular polyamines by the specific ODC-inhibitor α-difluoromethylornithine (DFMO) resulted in increased cellular binding of polyamine and anti-HS antibody. Importantly, anti-HS antibody also efficiently targeted DFMO-induced polyamine uptake, and combined polyamine biosynthesis inhibition by DFMO, and uptake inhibition by anti-HS antibody attenuated tumor cell proliferation in vitro. In conclusion, cell-surface HS proteoglycan is a relevant target for antibody-mediated inhibition of the uptake of polyamines, and polyamine-dependent cell proliferation.

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April 2008
Volume 32 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Welch JE, Bengtson P, Svensson K, Wittrup A, Jenniskens GJ, Ten Dam GB, Van Kuppevelt TH and Belting M: Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation. Int J Oncol 32: 749-756, 2008.
APA
Welch, J.E., Bengtson, P., Svensson, K., Wittrup, A., Jenniskens, G.J., Ten Dam, G.B. ... Belting, M. (2008). Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation. International Journal of Oncology, 32, 749-756. https://doi.org/10.3892/ijo.32.4.749
MLA
Welch, J. E., Bengtson, P., Svensson, K., Wittrup, A., Jenniskens, G. J., Ten Dam, G. B., Van Kuppevelt, T. H., Belting, M."Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation". International Journal of Oncology 32.4 (2008): 749-756.
Chicago
Welch, J. E., Bengtson, P., Svensson, K., Wittrup, A., Jenniskens, G. J., Ten Dam, G. B., Van Kuppevelt, T. H., Belting, M."Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation". International Journal of Oncology 32, no. 4 (2008): 749-756. https://doi.org/10.3892/ijo.32.4.749