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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 alpha-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.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Originalspråkengelska
Sidor (från-till)749-756
TidskriftInternational Journal of Oncology
Volym32
Utgåva nummer4
StatusPublished - 2008
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Svensson, K., 2012, Lund University: Faculty of Medicine. 160 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Welch, J., 2010, Department of Oncology, Clinical Sciences, Lund University. 158 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Anders Wittrup, 2009, Section of Oncology, Dept of Clinical Sciences.. 130 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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