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

• Main Authors: Mariana Costa Braga Schmidt, Katia L.P. Morais, Maíra Estanislau Soares de Almeida, Asif Iqbal, Mauricio Barbugiani Goldfeder, Ana Marisa Chudzinski-Tavassi
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2020-01-01
• Series: Cell Adhesion & Migration
• Subjects: amblyomin-x; kunitz-type inhibitor; cytoskeleton; migration; upar; rho-gtpase
• Online Access: http://dx.doi.org/10.1080/19336918.2018.1516982
• ISSN: 1933-6918; 1933-6926

In a tumor microenvironment, endothelial cell migration and angiogenesis allow cancer to spread to other organs causing metastasis.  Indeed, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling have been investigated for their effects on tumor cell growth and metastasis. Alongside that, Amblyomin-X, a recombinant Kunitz-type protein, has been shown to reduce metastasis and tumor growth in in vivo experiments. In the present report, we provide a mechanistic insight to these antitumor effects, this is,  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. Abbreviations Amb-X: Amblyomin-X; ECGF: endotelial cell growth factor; ECM: extracellular matrix; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cell; LRP1: low-density lipoprotein receptor-related protein; MMP: matrix metalloproteinase; HPI-4: hedgehog pathway inhibitor 4; PAI-1: plasminogen activator inhibitor 1; PMA: phorbol 12-myristate-13-acetate; TFPI: tissue factor pathway inhibitor; uPA: urokinase plasminogen activator; uPAR: uPA receptor.