Extracellular matrix-mediated chemotaxis can impede cell migration
Cells use a combination of changes in adhesion, proteolysis and motility (directed and random) during the process of migration. Proteolysis of the extracellular matrix (ECM) results in the creation of haptotactic gradients, which cells use to move in a directed fashion. The proteolytic creation of t...
| Asıl Yazarlar: | , , , , , , , |
|---|---|
| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
1998
|
| _version_ | 1826295256687050752 |
|---|---|
| author | Perumpanani, A Simmons, D Gearing, A Miller, K Ward, G Norbury, J Schneemann, M Sherratt, J |
| author_facet | Perumpanani, A Simmons, D Gearing, A Miller, K Ward, G Norbury, J Schneemann, M Sherratt, J |
| author_sort | Perumpanani, A |
| collection | OXFORD |
| description | Cells use a combination of changes in adhesion, proteolysis and motility (directed and random) during the process of migration. Proteolysis of the extracellular matrix (ECM) results in the creation of haptotactic gradients, which cells use to move in a directed fashion. The proteolytic creation of these gradients also results in the production of digested fragments of ECM. In this study we show that in the human fibrosarcoma cell line HT1080, matrix metallaproteinase-2 (MMP-2)-digested fragment of fibronectin exert a chemotactic pull stronger than that of undigested fibronectin. During invasion, this gradient of ECM fragments is established in the wake of an invading cell, running counter to the direction of invasion. The resultant chemotactic pull is anti-invasive, contrary to the traditional view of the role of chemotaxis in invasion. Uncontrolled ECM degradation by high concentrations of MMP can thus result in steep gradients of ECM fragments, which run against the direction of invasion. Consequently, the invasive potential of a cell depends on MMP production in a biphasic manner, implying that MMP inhibitors will upregulate invasion in high-MMP-expressing cells. Hence the therapeutic use of protease inhibitors against tumours expressing high levels of MMP could produce an augmentation of invasion. |
| first_indexed | 2024-03-07T03:58:14Z |
| format | Journal article |
| id | oxford-uuid:c39bf676-b06e-4fdb-a73b-9801baab344b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:58:14Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:c39bf676-b06e-4fdb-a73b-9801baab344b2022-03-27T06:17:45ZExtracellular matrix-mediated chemotaxis can impede cell migrationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c39bf676-b06e-4fdb-a73b-9801baab344bEnglishSymplectic Elements at Oxford1998Perumpanani, ASimmons, DGearing, AMiller, KWard, GNorbury, JSchneemann, MSherratt, JCells use a combination of changes in adhesion, proteolysis and motility (directed and random) during the process of migration. Proteolysis of the extracellular matrix (ECM) results in the creation of haptotactic gradients, which cells use to move in a directed fashion. The proteolytic creation of these gradients also results in the production of digested fragments of ECM. In this study we show that in the human fibrosarcoma cell line HT1080, matrix metallaproteinase-2 (MMP-2)-digested fragment of fibronectin exert a chemotactic pull stronger than that of undigested fibronectin. During invasion, this gradient of ECM fragments is established in the wake of an invading cell, running counter to the direction of invasion. The resultant chemotactic pull is anti-invasive, contrary to the traditional view of the role of chemotaxis in invasion. Uncontrolled ECM degradation by high concentrations of MMP can thus result in steep gradients of ECM fragments, which run against the direction of invasion. Consequently, the invasive potential of a cell depends on MMP production in a biphasic manner, implying that MMP inhibitors will upregulate invasion in high-MMP-expressing cells. Hence the therapeutic use of protease inhibitors against tumours expressing high levels of MMP could produce an augmentation of invasion. |
| spellingShingle | Perumpanani, A Simmons, D Gearing, A Miller, K Ward, G Norbury, J Schneemann, M Sherratt, J Extracellular matrix-mediated chemotaxis can impede cell migration |
| title | Extracellular matrix-mediated chemotaxis can impede cell migration |
| title_full | Extracellular matrix-mediated chemotaxis can impede cell migration |
| title_fullStr | Extracellular matrix-mediated chemotaxis can impede cell migration |
| title_full_unstemmed | Extracellular matrix-mediated chemotaxis can impede cell migration |
| title_short | Extracellular matrix-mediated chemotaxis can impede cell migration |
| title_sort | extracellular matrix mediated chemotaxis can impede cell migration |
| work_keys_str_mv | AT perumpanania extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT simmonsd extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT gearinga extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT millerk extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT wardg extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT norburyj extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT schneemannm extracellularmatrixmediatedchemotaxiscanimpedecellmigration AT sherrattj extracellularmatrixmediatedchemotaxiscanimpedecellmigration |