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

Author(s)

Schmidt, Mariana Costa Braga ^{[1, 2]} ; Morais, Katia L. P. ^{[1, 2, 3]} ; de Almeida, Maira Estanislau Soares ^{[2, 3]} ; Iqbal, Asif ^{[2, 3]} ; Goldfeder, Mauricio Barbugiani ^{[2, 3]} ; Chudzinski-Tavassi, Ana Marisa ^{[1, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[2] Butantan Inst, Lab Mol Biol, Ave Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[3] Butantan Inst, Ctr Excellence New Target Discovery, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELL ADHESION & MIGRATION; v. 14, n. 1, p. 129-138, JAN 1 2020.
• Web of Science Citations: 6

Abstract

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. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/24512-3 - Evaluation of Ambiyomin-X effect in activation of endothelial cells by tumor microenvironment
• Grantee: Mariana Costa Braga Schmidt
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support type: Research Grants - Research Centers in Engineering Program