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Differences in the uptake and nuclear localization of anti-proliferative heparan sulfate between human lung fibroblasts and human lung carcinoma cells

In English

Författare

Summary, in English

Heparan sulfate inhibits the proliferation of normal human lung fibroblasts (HFL-1) but not of a human lung carcinoma cell-line (A549). in this study we investigated possible mechanisms and structural requirements by which anti proliferative heparan sulfates exerts its effects on binding, uptake and subcellular localisation. Both HFL-1 and A549 cells were incubated with I-125- or rhodamine-labeled L-iduronate-rich antiproliferative heparan sulfate species as well as L-iduronate-poor inactive ones. The anti proliferative heparan sulfate was bound to the cell surface on both HFL-1 and A549 cells, but to a lesser extent and with less affinity to A549 cells. Both cell types bound the anti proliferative heparan sulfate with one high- and with one low affinity site. The L-iduronate-poor heparan sulfate bound to a lesser extent and with less affinity to both cell types compared to the anti proliferative heparan sulfate. The antiproliferative heparan sulfate accumulated in the cytoplasm of HFL-1 cells after 24 h incubation, but after 72 h it was found evenly distributed in the nucleus. The time-scale for anti proliferative activity correlated with nuclear localization. In contrast, in A549 cells it was only found near the nuclear membrane. The inactive heparan sulfate was taken up in considerably smaller amounts compared to the antiproliferative heparan sulfate and could not be detected in the nucleus of either HFL-1 or A549 cells. Our data suggest that the anti proliferative activity of L-iduronate-rich heparan sulfate on normal fibroblasts may be due to direct effects on nuclear processes, such as gene transcription.

Publiceringsår

2001

Språk

Engelska

Sidor

597-606

Publikation/Tidskrift/Serie

Journal of Cellular Biochemistry

Volym

83

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Neurosciences
  • Cell and Molecular Biology
  • Medicinal Chemistry

Nyckelord

  • antiproliferative activity
  • heparan sulfate
  • nuclear localization
  • confocal microscopy

Status

Published

Forskningsgrupp

  • Glycobiology
  • Neurophysiology
  • Lung Biology

ISBN/ISSN/Övrigt

  • ISSN: 0730-2312