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.  Indeed, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling have been investigated for their effects on tumor cell grow...

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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:
Online Access:http://dx.doi.org/10.1080/19336918.2018.1516982
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spelling doaj-35401d0a63a6462bbc1acd054738cfdb2021-01-04T18:02:33ZengTaylor & Francis GroupCell Adhesion & Migration1933-69181933-69262020-01-0114112913810.1080/19336918.2018.15169821516982Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cellsMariana Costa Braga Schmidt0Katia L.P. Morais1Maíra Estanislau Soares de Almeida2Asif Iqbal3Mauricio Barbugiani Goldfeder4Ana Marisa Chudzinski-Tavassi5Butantan InstituteButantan InstituteButantan InstituteButantan InstituteButantan InstituteButantan InstituteIn 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.http://dx.doi.org/10.1080/19336918.2018.1516982amblyomin-xkunitz-type inhibitorcytoskeletonmigrationuparrho-gtpase
collection DOAJ
language English
format Article
sources DOAJ
author Mariana Costa Braga Schmidt
Katia L.P. Morais
Maíra Estanislau Soares de Almeida
Asif Iqbal
Mauricio Barbugiani Goldfeder
Ana Marisa Chudzinski-Tavassi
spellingShingle Mariana Costa Braga Schmidt
Katia L.P. Morais
Maíra Estanislau Soares de Almeida
Asif Iqbal
Mauricio Barbugiani Goldfeder
Ana Marisa Chudzinski-Tavassi
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
Cell Adhesion & Migration
amblyomin-x
kunitz-type inhibitor
cytoskeleton
migration
upar
rho-gtpase
author_facet Mariana Costa Braga Schmidt
Katia L.P. Morais
Maíra Estanislau Soares de Almeida
Asif Iqbal
Mauricio Barbugiani Goldfeder
Ana Marisa Chudzinski-Tavassi
author_sort Mariana Costa Braga Schmidt
title Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
title_short Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
title_full Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
title_fullStr Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
title_full_unstemmed Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
title_sort amblyomin-x, a recombinant kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
publisher Taylor & Francis Group
series Cell Adhesion & Migration
issn 1933-6918
1933-6926
publishDate 2020-01-01
description 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.
topic amblyomin-x
kunitz-type inhibitor
cytoskeleton
migration
upar
rho-gtpase
url http://dx.doi.org/10.1080/19336918.2018.1516982
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