In vitro study of low molecular weight heparin effect on cell growth and cell invasion in primary cell cultures of high-grade gliomas

Marco Balzarotti, Federica Fontana, Carlo Marras, Amerigo Boiardi, Danilo Croci, Emilio Ciusani, Andrea Salmaggi

Research output: Contribution to journalArticle

Abstract

Heparins represent the first choice for prevention and treatment of venous thromboembolism. In particular, low molecular weight heparins (LMWHs) provide pharmacokinetic advantages compared to unfractionated heparin (UFH): longer half-life, better bioavailability, and lower binding to plasma proteins. In the last years results of preclinical and clinical studies have suggested that LMWH may be able to inhibit cell growth, cell invasion, and angiogenesis, which are key mechanisms involved in tumor progression, possibly influencing favorable clinical outcome in at least a proportion of cancer patients. In this work we investigated the effect of LMWH (enoxaparin) on cell growth and cell invasion in primary cell cultures obtained from high-grade glioma specimens: 5 anaplastic astrocytoma (AA) and 13 glioblastoma multiforme (GBM). Apoptosis and expression of the thrombin receptor PAR1 were also assessed. A significant decrease in tumor cell growth was observed after treatment with 10 U/ml (-21%; p = 0.001) and 100 U/ml (-26%; p <0.001); tumor cells from AA (grade III; WHO) were more affected by LMWH treatment compared to cell lines from GBM (grade IV; WHO). The antiproliferative effect was more pronounced in cell cultures displaying higher expression of PAR1. Glioma cell cultures were able to invade a model of basement membrane (Matrigel™ matrix) in standard culture conditions, but migration was not modulated significantly by LMWH treatment at any of the concentrations tested (1, 10, 100 U/ml). In conclusion, our results confirm the antineoplastic effect of LMWH, suggesting a potential direct role on tumor cell growth in high grade gliomas.

Original languageEnglish
Pages (from-to)245-250
Number of pages6
JournalOncology Research
Volume16
Issue number5
Publication statusPublished - 2006

Keywords

  • Glioma
  • Invasion
  • Low molecular weight heparin (LMWH)
  • Primary cell cultures

ASJC Scopus subject areas

  • Cancer Research

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