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...
| Main Authors: | , , , , , |
|---|---|
| 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 |
| _version_ | 1818669166190657536 |
|---|---|
| author | Mariana Costa Braga Schmidt Katia L.P. Morais Maíra Estanislau Soares de Almeida Asif Iqbal Mauricio Barbugiani Goldfeder Ana Marisa Chudzinski-Tavassi |
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T06:47:53Z |
| format | Article |
| id | doaj.art-35401d0a63a6462bbc1acd054738cfdb |
| institution | Directory Open Access Journal |
| issn | 1933-6918 1933-6926 |
| language | English |
| last_indexed | 2024-12-17T06:47:53Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cell Adhesion & Migration |
| spelling | doaj.art-35401d0a63a6462bbc1acd054738cfdb2022-12-21T21:59:41ZengTaylor & 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 |
| 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 |
| title | 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_short | 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 |
| topic | amblyomin-x kunitz-type inhibitor cytoskeleton migration upar rho-gtpase |
| url | http://dx.doi.org/10.1080/19336918.2018.1516982 |
| work_keys_str_mv | AT marianacostabragaschmidt amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells AT katialpmorais amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells AT mairaestanislausoaresdealmeida amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells AT asifiqbal amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells AT mauriciobarbugianigoldfeder amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells AT anamarisachudzinskitavassi amblyominxarecombinantkunitztypeinhibitorregulatescelladhesionandmigrationofhumantumorcells |