Objective       To determine the effect of high expression of heparanase (HPSE) in hepatocellular carcinoma (HCC) cells on the formation of portal venous microemboli (PVME) in HCC nude mice.  Methods       HCCLM3 cells with high expres

sion of HPSE and HepG2 cells with relatively low expression of HPSE were selected basing on our previous study. Nude mice were intraperitoneally injected with 300 μL of HCC cells (3×10

6

cells)

  and the tumor formation in the omentum and liver were respectively observed in 3 and 5 weeks after injection. The vessel invasion and PVME were observed by microscopy. After the HCC models were established

the nude mice were subcutaneously injected with heparin sodium at a dose of 250 IU once per 3 d for 2 weeks in 2 weeks after HCC cells injection

and normal sodium was used for control.  Results        All nude mice survived without obvious changes in diet and activity

and their weight significantly increased in the 3rd week (P0.05). For the 2 kinds of HCC cells

the tumor formation rate was both 5/5 in the omentum at the 3rd and 5th weeks. The tumor formation rate of HCCLM3 cells in the liver  was significantly higher than that of HepG2 cells at the 3rd week (2/5 vs 0/5

P0.05)

and the rates of the 2 kinds of cells were similar at the 5th week (5/5 vs 4/5)

but the tumor sizes were larger in those induced by HCCLM3 cells. At the the 3rd and 5th weeks

HCCLM3 cells mediated more vessel invasions in the omentum and portal vein than HepG2 cells (2/5 vs 0/5

5/5 vs 3/5

both P0.05). PVME rate was similar in the HCCLM3 cells and HepG2 cells at the 3rd week (1/5 vs 0/5)

but significantly higher in the former than the latter cells at the 5th week (5/5 vs 0/5

P0.05). Subcutaneous injection of heparin for 2 weeks attenuated the omentum and liver metastases

vessel invasion and PVME in the HCCLM3 cells group compared with normal sodium group at the 3rd week (all P0.05). HepG2 cells induced omentum metastasis was also decreased obviously (P0.05). After heparin was withdrawn

liver metastases were found again in the 2 kinds of models at the 5th week

and HCCLM3 cells mediated PVME appeared once again. HCCLM3 cells induced the omentum and liver metastases

vessel invasion and PVME in heparin group were all less than

normal sodium group (all P0.05). Conclusion       Intraperitoneal injection of HPSE highlyexpressed HCCLM3 cells can successfully mediate the formation of PVME in nude mice HCC model. HPSE may be one of important factors of PVME formation.