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

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 16, Number 5, 2006 , pp. 245-250(6)

Publisher: Cognizant Communication Corporation

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^TM 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.

Keywords: Primary cell cultures; Glioma; Low molecular weight heparin (LMWH); Invasion

Document Type: Research article

Affiliations: 1: Laboratory of Clinical Investigation, Department of Neurology, Department of Neurosurgery, National Neurological Institute “C. Besta,” Via Celoria 11, 20133 Milan, Italy

Publication date: 2006-05-01

More about this publication?

• Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
  Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

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