The Hypoxia-inducible-factor-1 (HIF-1)-signaling pathway regulates the cellular adaptation of tumor cells to stress thereby securing their survival. So far it has not been shown that HIF-1 directly regulates tumor cell invasiveness in addition to conferring a survival advantage to metastasizing tumor cells. Survival of the aggressive murine tumor cell line L-CI.5s was unaffected by knockdown of HIF-1α therefore being an ideal model for uncovering the importance of HIF-1 for the invasive potential of tumor cells and the underlying mechanism, which was the activation of pro-invasive Met-signaling as well as expression of MMP-9. A Met specific antibody was found to inhibit the HIF-1-mediated induction of the Met-pathway and the Met-dependent mobilization of tumor cells by inducing an ADAM-10-mediated shedding of the Met-receptor. Therefore, this therapeutic approach is a chance to inhibit HIF-1-mediated metastasis without interfering with the multiplicity of HIF-1-regulated processes.      «

The Hypoxia-inducible-factor-1 (HIF-1)-signaling pathway regulates the cellular adaptation of tumor cells to stress thereby securing their survival. So far it has not been shown that HIF-1 directly regulates tumor cell invasiveness in addition to conferring a survival advantage to metastasizing tumor cells. Survival of the aggressive murine tumor cell line L-CI.5s was unaffected by knockdown of HIF-1α therefore being an ideal model for uncovering the importance of HIF-1 for the invasive potentia...     »