Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells.
Autor: Schmidt, Mariana Costa Braga; Morais, Katia L. P.; Almeida, Maíra Estanislau Soares de; Iqbal, Asif; Goldfeder, Mauricio Barbugiani; Chudzinski-Tavassi, Ana Marisa
Publication year: 2020
Cell adhesion & migration
issn:1933-6926 1933-6918
doi: 10.1080/19336918.2018.1516982
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. 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.
Language: eng
Rights:
Pmid: 30238848
Tags: Humans; Cell Line, Tumor; Cell Survival/drug effects; migration; cytoskeleton; Cell Adhesion/drug effects; Cell Death/drug effects; Amblyomin-X; Aprotinin/*pharmacology; Arthropod Proteins/*pharmacology; Cell Movement/*drug effects; Cytoskeleton/drug effects/metabolism; Kunitz-type inhibitor; Matrix Metalloproteinases/metabolism; Receptors, Urokinase Plasminogen Activator/metabolism; Recombinant Proteins/*pharmacology; rho GTP-Binding Proteins/metabolism; Rho-GTPase; Salivary Proteins and Peptides/*pharmacology; uPAR
Link: https://pubmed.ncbi.nlm.nih.gov/30238848/
