Basic HGF-like peptides inhibit generation of liver metastases in murine and human tumor models

We have postulated that the peptide domain(s) of the heparin-binding cytokine(s) might have biological activity, which theoretically could be exploited for modulation of the biological behavior of cancer cells.

We used HGF as a model heparin-binding cytokine and synthesized two HGF beta-chain domains, HHRGK (HGP1) and RYRNKH (HGP2), as well as four variants. As target cells, we used three cancer cell lines (HT25 human colonic, HT168-M1/9 human melanoma and 3LL-HH murine lung carcinoma) all characterized by strong liver metastatic potentials. The effects of peptides on cell proliferation, tumor growth and liver metastasis were evaluated.

All the basic penta- or hexapeptides exhibited similar antiproliferative effects in vitro in a dose range of 100-1000 ng/ml. Meanwhile, none of the HGP peptides exhibited significant antitumoral effects on the primary spleen tumors in the form of systemic treatment. However, systemic treatment with HGP1, but not with HGP2, applied at the early phase of the dissemination process, showed an inhibitory effect on liver metastatization of all the tumor lines studied. Furthermore, one out of the four hexapeptides, BP4 (KRKRKR), had similar activity.

Recent data on the antiangiogenic effects of these basic peptides partially explain the in vivo antimetastatic activity. We suggest the small basic penta-hexapeptides as a new class of biological response modifiers which can modulate the metastatic process.