Mariana Costa Braga Schmidt, Katia L P Morais, Maíra Estanislau Soares de Almeida, Asif Iqbal, Mauricio Barbugiani Goldfeder, Ana Marisa Chudzinski-Tavassi
{"title":"Amblyomin-X是一种重组kunitz型抑制剂,可调节人肿瘤细胞的粘附和迁移。","authors":"Mariana Costa Braga Schmidt, Katia L P Morais, Maíra Estanislau Soares de Almeida, Asif Iqbal, Mauricio Barbugiani Goldfeder, Ana Marisa Chudzinski-Tavassi","doi":"10.1080/19336918.2018.1516982","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p><p><strong>Abbreviations: </strong>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.</p>","PeriodicalId":9680,"journal":{"name":"Cell Adhesion & Migration","volume":"14 1","pages":"129-138"},"PeriodicalIF":3.3000,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19336918.2018.1516982","citationCount":"11","resultStr":"{\"title\":\"Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells.\",\"authors\":\"Mariana Costa Braga Schmidt, Katia L P Morais, Maíra Estanislau Soares de Almeida, Asif Iqbal, Mauricio Barbugiani Goldfeder, Ana Marisa Chudzinski-Tavassi\",\"doi\":\"10.1080/19336918.2018.1516982\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p><p><strong>Abbreviations: </strong>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.</p>\",\"PeriodicalId\":9680,\"journal\":{\"name\":\"Cell Adhesion & Migration\",\"volume\":\"14 1\",\"pages\":\"129-138\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2020-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/19336918.2018.1516982\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Adhesion & Migration\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/19336918.2018.1516982\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/9/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Adhesion & Migration","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/19336918.2018.1516982","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/9/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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 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.
期刊介绍:
Cell Adhesion & Migration is a multi-disciplinary, peer reviewed open access journal that focuses on the biological or pathological implications of cell-cell and cell-microenvironment interactions. The main focus of this journal is fundamental science. The journal strives to serve a broad readership by regularly publishing review articles covering specific disciplines within the field, and by publishing focused issues that provide an overview on specific topics of interest within the field.
Cell Adhesion & Migration publishes relevant and timely original research, as well as authoritative overviews, commentaries, and perspectives, providing context for the work presented in Cell Adhesion & Migration and for key results published elsewhere. Original research papers may cover all topics important in the field of cell-cell and cell-matrix interactions. Cell Adhesion & Migration also publishes articles related to cell biomechanics, biomaterial, and development of related imaging technologies.