As compared to vector control, there was a significant increase in cell proliferation by 25%. Suppression of Pyk2 signalling by PRNK significantly delayed the proliferation of PLC cells in presence of serum. There was a 20% decrease in the rate of proliferation of PLC-PRNK cells as compared to vector control. These results suggested that Pyk2 was involved download the handbook in the proliferation of PLC cells. Pyk2 expression promotes Matrigel invasion In addition to promotion of cancer cell proliferation, Pyk2 also increased the tumour cell invasiveness detected by the three-dimensional invasion assays. Pyk2 transfectants had higher ability to degrade and move through the matrigel (Figure 6B). Normal PLC cells exhibited the ability to invade the Matrigel. Pyk2 transfectants had 10-fold increased invasion compared to vector control.

These results show that Pyk2 promoted an invasive phenotype in PLC cells but not in vector control and PRNK transfectants where the signalling of Pyk2 is being disrupted. Protein expression of Pyk2 in liver tumour and lung metastatic nodule in an orthotopic liver tumour model in nude mice: overexpression of Pyk2 correlated with tumour invasiveness and metastasis To further confirm the significance of Pyk2 in HCC invasiveness, we detected the protein expression of Pyk2 in the liver tumour and metastatic nodules in an orthotopic liver tumour model in nude mice. In the orthotopic liver tumour nude mice model with higher potential of local (intrahepatic) and distant (lung) metastases, strong positive staining of Pyk2 was found in tumour cells with infiltrative growth pattern (Figure 7A).

The lung metastatic nodule from the nude mice bearing liver tumour also expressed Pyk2 (Figure 7B). Therefore, the overexpression Batimastat of Pyk2 was consistent with the aggressive features of the tumour cells. Figure 7 Proline-rich kinase 2 expression of the liver tumour (A) and lung metastatic nodule (B, arrow) in a nude mice orthotopic liver tumour model with higher potential of local and distant metastases. DISCUSSION Development of novel therapies for liver cancer metastases and recurrence is always essential to achieve the long-term survival after curative surgical resection (Tung-Ping et al, 2000). Cell migration and invasion are fundamental components of tumour recurrence and metastasis. Understanding the precise molecular mechanism of cancer cell migration and invasion will be important to develop novel therapeutic strategies targeting tumour metastasis and recurrence and to increase the sensitivity of current treatment modalities. Proline-rich tyrosine kinase 2 and FAK play pivotal roles in the regulation of cell motility and invasion (Sasaki et al, 1995; Sieg et al, 2000; Fujii et al, 2004; Itoh et al, 2004; van Nimwegen et al, 2005).