Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells

In a tumor microenvironment, endothelial cell migration and angiogenesis allow cancer to spread to other organs causing metastasis. This event is regulated by proteinases that induce extracellular matrix degradation and cell-substratum detachment. In this sense, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling, including uPA its receptor uPAR as well as Rho-GTPases, have been investigated for their effects on tumor cell growth and metastasis. Along the same line, Amblyomin-X, a recombinant Kunitz-type protein, has been shown to reduce metastasis and tumor growth in <i>in vivo</i> experiments. In the present report, we provide a mechanistic insight to these antitumor effects. We demonstrate that Amblyomin-X modulates Rho-GTPases and uPAR signaling, and reduces the release of MMPs, leading to disruption of the actin cytoskeleton and decreased cell migration of tumor cell lines. Altogether, our data support a role for Amblyomin-X as a novel potential antitumor drug.