Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner
Esophageal cancer, which frequently exhibits coordinated loss of E-cadherin (Ecad) and transforming growth factor β (TGFβ) receptor II (TβRII), has a high mortality rate. In a three-dimensional organotypic culture model system, esophageal keratinocytes expressing dominant-negative mutant versions of...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558610800065 |
| _version_ | 1819141199346270208 |
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| author | Claudia D. Andl Kelsey M. McCowan Gillian L. Allison Anil K. Rustgi |
| author_facet | Claudia D. Andl Kelsey M. McCowan Gillian L. Allison Anil K. Rustgi |
| author_sort | Claudia D. Andl |
| collection | DOAJ |
| description | Esophageal cancer, which frequently exhibits coordinated loss of E-cadherin (Ecad) and transforming growth factor β (TGFβ) receptor II (TβRII), has a high mortality rate. In a three-dimensional organotypic culture model system, esophageal keratinocytes expressing dominant-negative mutant versions of both Ecad and TβRII (ECdnT) invade into the underlying matrix embedded with fibroblasts. We also find that cathepsin B induction is necessary for fibroblast-mediated invasion. Furthermore, the ECdnT cells in this physiological context activate fibroblasts through the secretion of TGFβ1, which, in turn, is activated by cathepsin B. These results suggest that the interplay between the epithelial compartment and the surrounding microenvironment is crucial to invasion into the extracellular matrix. |
| first_indexed | 2024-12-22T11:50:39Z |
| format | Article |
| id | doaj.art-9849596275bf46cf8166ca70500189f2 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-22T11:50:39Z |
| publishDate | 2010-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-9849596275bf46cf8166ca70500189f22022-12-21T18:27:00ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022010-06-0112648549810.1593/neo.10216Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent MannerClaudia D. Andl0Kelsey M. McCowan1Gillian L. Allison2Anil K. Rustgi3Departments of Surgery and Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USADepartments of Surgery and Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USADepartments of Surgery and Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USAGastroenterology Division, Departments of Medicine and Genetics, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USAEsophageal cancer, which frequently exhibits coordinated loss of E-cadherin (Ecad) and transforming growth factor β (TGFβ) receptor II (TβRII), has a high mortality rate. In a three-dimensional organotypic culture model system, esophageal keratinocytes expressing dominant-negative mutant versions of both Ecad and TβRII (ECdnT) invade into the underlying matrix embedded with fibroblasts. We also find that cathepsin B induction is necessary for fibroblast-mediated invasion. Furthermore, the ECdnT cells in this physiological context activate fibroblasts through the secretion of TGFβ1, which, in turn, is activated by cathepsin B. These results suggest that the interplay between the epithelial compartment and the surrounding microenvironment is crucial to invasion into the extracellular matrix.http://www.sciencedirect.com/science/article/pii/S1476558610800065 |
| spellingShingle | Claudia D. Andl Kelsey M. McCowan Gillian L. Allison Anil K. Rustgi Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner Neoplasia: An International Journal for Oncology Research |
| title | Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner |
| title_full | Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner |
| title_fullStr | Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner |
| title_full_unstemmed | Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner |
| title_short | Cathepsin B Is the Driving Force of Esophageal Cell Invasion in a Fibroblast-Dependent Manner |
| title_sort | cathepsin b is the driving force of esophageal cell invasion in a fibroblast dependent manner |
| url | http://www.sciencedirect.com/science/article/pii/S1476558610800065 |
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