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Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation.
Welch, Johanna E; Bengtson, Per; Svensson, Katrin; Wittrup, Anders; Jenniskens, Guido J; Ten Dam, Gerdy B; Van Kuppevelt, Toin H; Belting, Mattias.
Afiliação
  • Welch JE; Department of Clinical Sciences, Division of Oncology, Lund University, SE-22185, Lund, Sweden.
Int J Oncol ; 32(4): 749-56, 2008 Apr.
Article em En | MEDLINE | ID: mdl-18360702
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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Imunoglobulinas / Poliaminas Biogênicas / Heparitina Sulfato Limite: Animals / Humans Idioma: En Revista: Int J Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Suécia País de publicação: Grécia
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fragmentos de Imunoglobulinas / Poliaminas Biogênicas / Heparitina Sulfato Limite: Animals / Humans Idioma: En Revista: Int J Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Suécia País de publicação: Grécia