Proline-rich antimicrobial peptide, PR-39 gene transduction altered invasive activity and actin structure in human hepatocellular carcinoma cells

PR-39 is an endogenous proline-rich antimicrobial peptide which induces the synthesis of syndecan-1, a transmembrane heparan sulphate proteoglycan inv olved in cell-to-matrix interactions and wound healing. Previously, we reve aled that the expression of syndecan-1 was reduced in human hepatocellular carcinomas with high metastatic potential and speculated that syndecan-1 pl ayed an important role in inhibition of invasion and metastasis. It is assu med that a modification of this; process with PR-39 and syndecan-1 may resu lt in a new strategy by which it can inhibit the invasion and metastasis. T herefore, we transduced a gene of PR-39 into human hepatocellular carcinoma cell line HLF, which shows a low expression of syndecan-1 and a high in vi tro invasive activity, and examined whether this procedure could reduce the invasive activity of tumour cells. In two transfectants with PR-39 gene, t he syndecan-1 expression was induced and the invasive activity in type I co llagen-coated chamber was inhibited. Moreover, these transfectants showed t he suppression of motile activity assayed by phagokinetic tracks in additio n to the disorganization of actin filaments observed by a confocal imaging system. In contrast, five transfectants with syndecan-1 gene in the HLF cel ls revealed suppression of invasive activity but did not alter the motile a ctivity and actin structures of the cell. These results suggest that PR-39 has functions involved in the suppression of motile activity and alteration of actin structure on human hepatocellular carcinoma cells in addition to the suppression of invasive activity which might result from the induction of syndecan-1 expression. (C) 1999 Cancer Research Campaign.