INFLUENCE OF ANGIOSTATIN AND THALIDOMIDE ON LYMPHANGIOGENESIS

Abstract

Malignant cancers commonly invadelocally followed by spread through venous orlymphatic channels or both to distant sites.Hemangiogenesis and its relation to tumorgrowth and metastasis have been extensivelystudied. However, the role played by lymphangiogenesisin growth and metastasis of cancerhas been largely neglected until just recently.Inhibition of lymphangiogenesis, as comparedto inhibition of hemangiogenesis, may providenew insights into the mechanisms of cancermetastasis. The current study was designed toexamine the in vitro effect of two commonlyused inhibitors of hemangiogenesis, angiostatinand thalidomide, on the growth and proliferationof lymphatic endothelial cells isolatedfrom pig thoracic ducts. We first isolated andcharacterized the lymphatic endothelial (LE)cells using specific markers for VEGFR3 andLYVE-1. The experimental results showedthat treatment of the LE cells with these twodrugs resulted in a decrease in the rate of cellproliferation in a dose-dependent manner asassessed by MTT assays. Cell migration ratewas assessed by the speed of cell migrationfrom the scrape-wound margin, and theresults showed that migration of LE cells wasalso significantly inhibited in a dose-dependentfashion compared to controls. Treatment withangiostatin and thalidomide both resulted inan increase in apoptosis of LE cells as assessedby Hoechst staining and flow cytometry. Weconclude that both angiostatin and thalidomideare able to inhibit LE cell growth in a dosedependentmanner and that the inhibition maybe through induction of apoptosis.