Influence of IFN- alpha and IFN- gamma on lymphangiogenesis.

ABSTRACT

Malignant cancers commonly spread by local invasion followed by metastasis through venous or lymphatic passages or both to distant sites. Angiogenesis and its relation to tumor growth and metastasis have been extensively researched. To date, however, the role played by lymphangiogenesis and metastasis of cancer has been overlooked. Inhibition of lymphangiogenesis, compared with inhibition of angiogenesis, may provide new insight to the mechanisms of metastasis of cancers. The current study was designed to examine the effect of two commonly used inhibitors of angiogenesis, interferon-alpha (IFN-alpha ) and IFN-gamma, on the growth and proliferation of lymphatic endothelial (LE) cells isolated from pig thoracic duct under in vitro condition. The LE cells were isolated and marked using specific markers, such as VEGFR-3 and LYVE-1, before experimental studies. The results showed that treatment of LE cells derived from the thoracic duct with these two inhibitors caused a decrease in the rate of cell proliferation in a dose-dependent manner, as assessed by MTT assays (tetrazolium salt colorimetric assay). Cell migration rate was assessed by the speed at which the cell migrated out from the scrape-wound margin; the speed of migration of LE cells was significantly inhibited in a dose-dependent fashion compared with controls. Treatment with both IFN-alpha and IFN-gamma caused an increase in apoptosis of LE cells, as assessed by Hoechst staining and caspase-3 staining. Our results showed that both IFN-alpha and IFN-gamma were able to inhibit LE cell growth in a dose-dependent manner and that the inhibition may be through induction of apoptosis of endothelial cells.