Hepatocyte growth factor (HGF), a potent cytokine of mesenchymal origin, exhibits polytrophic physiological responses, including proliferation, migration, and invasion, in a wide variety of cells. Although it is known that inhibition of the responses by HGF variants was via signal transducers and activators of the transcription pathway, the mechanisms of action of the variants involved in the production of matrix metalloproteinases (MMPs) were not clearly understood. Thus, recombinant HGF variants, NK1, NK2, NK3, and NK4 were topically applied to assays for proliferation, migration, invasion, and expression of MMPs in the human lung cancer cell line A549 and compared to that of control medium and a glutathione-s-transferase control. Results showed that these recombinant HGF variants significantly inhibited proliferation, migration, and invasion of A549 at >4 nM, downregulated expression of MMP-9, and upregulated expression of MMP-8. The study clearly suggests that binding of the HGF variants to the cell surface c-Met resulted in the downregulation of MMP-9, and upregulation of MMP-8 protein expressions might be key molecular signals against proliferation, migration, and invasion of A549 cells.

Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its receptor, and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.