Abstract
BackgroundThrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. The aim was to examine the effects of platelets in relation to HCC cell growth.MethodsThe effects of time-expired pooled normal human platelets were examined on human HCC cell line growth and invasion.ResultsBlood platelet numbers increased with increasing HCC tumor size and portal vein invasion. Platelet extracts enhanced cell growth in 4 human HCC cell lines, as well as cell migration, medium AFP levels and decreased apoptosis. Cell invasion was significantly enhanced, using a Matrigel-coated trans-well membrane and3D (Real-Time Imaging) invasion assay. Western blots showed that platelets caused enhanced phospho-ERK and phospho–JNK signaling and anti-apoptotic effect with increase of Bcl-xL (anti-apoptotic marker) and decrease of Bid (pro-apoptotic marker) levels. Their growth effects were blocked by a JNK inhibitor.ConclusionsPlatelets stimulated growth and invasion of several HCC cell lines in vitro, suggesting that platelets or platelet growth factors could be a potential pharmacological target.
Highlights
Thrombocytopenia has been reported to be associated with small size hepatocellular carcinoma (HCC), and thrombocytosis to be associated with large size HCCs
Platelets as a source of HCC growth stimulants Human Platelets lysates (hPL) were examined for the ability to stimulate human HCC cell line growth
PLC/RFP/5 cells were cultured in different FBS concentrations (0-5%) for 48h in presence of hPL or equivalent FBS concentration in order to define the minimum FBS concentration to maintain the health of cells without growth
Summary
Thrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. Cancer can result in altered coagulation and platelet activity and platelets have the ability to influence cancer growth and metastasis [2,5] This can occur by direct platelet effects or through mesenchymal interactions [6,7]. Thrombocytopenia of cirrhosis has recently been shown to be associated predominantly with small size HCCs [11], whereas very large size HCCs often have normal platelet counts [12] and thrombocytosis in HCC patients occurs most often with large size tumors [13]. We have examined the effects of platelet extracts on the growth in vitro of human HCC cell lines and report that they enhance cell proliferation, migration and invasion
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