Evidence of a bi-phasic effect of thrombospondin-1 on angiogenesis

Katsumi Motegi, Koji Harada, Sima Pazouki, Robin Baillie, Ana M. Schor

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Abstract

Contradictory results have been reported regarding the association between vascularity (used as an index of angiogenesis) and thrombospondin-1 (TSP-1) in human tumours. In previous studies, the reported association was based on the estimated average TSP-1 value per tumour, with a sufficient number of specimens collectively analysed per tumour type. Given the extent of intra-tumour heterogeneity, we determined the association between TSP-1 and vascularity within individual specimens, based on the average values of TSP-1 and vascularity in 10–20 pre-selected areas per tumour. Cells expressing TSP-1 mRNA were visualised by in situ hybridisation and quantified by point counting. Vascularity was quantified by point counting and vessel density of von Willebrand Factor-positive vessels. In 10 ductal breast carcinomas, a direct correlation between TSP-1 and vascularity was found in 4 tumours, no correlation in 3 and an inverse correlation in 3. The effect of TSP-1 on endothelial cell migration in vitro was assessed in the Boyden chamber assay. TSP-1 stimulated cell migration at low concentrations (0.1–10?µg/ml) and was inhibitory at high concentrations (25–100?µg/ml). These results suggest that TSP-1 may elicit a concentration-dependent, bi-phasic, effect on angiogenesis.
Original languageEnglish
Pages (from-to)411-421
Number of pages11
JournalHistochemical Journal
Volume34
Issue number8-9
DOIs
Publication statusPublished - Sep 2002

Keywords

  • Endothelial Cell Migration
  • Boyden Chamber Assay
  • Calibration Slide
  • Endothelial Cell Heterogeneity
  • Stromal Index

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    Motegi, K., Harada, K., Pazouki, S., Baillie, R., & Schor, A. M. (2002). Evidence of a bi-phasic effect of thrombospondin-1 on angiogenesis. Histochemical Journal, 34(8-9), 411-421. https://doi.org/10.1023/A:1023687505139