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dc.contributor.authorBates, Richard C.
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:01.000
dc.date.accessioned2022-08-23T15:39:46Z
dc.date.available2022-08-23T15:39:46Z
dc.date.issued2003-06-13
dc.date.submitted2010-11-07
dc.identifier.citationMol Biol Cell. 2003 May;14(5):1790-800. Epub 2003 Jan 26. <a href="http://dx.doi.org/10.1091/mbc.E02-09-0583">Link to article on publisher's site</a>
dc.identifier.issn1059-1524 (Linking)
dc.identifier.doi10.1091/mbc.E02-09-0583
dc.identifier.pmid12802055
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26248
dc.description.abstractAn epithelial-mesenchymal transition (EMT) characterizes the progression of many carcinomas and it is linked to the acquisition of an invasive phenotype. Given that the tumor microenvironment is an active participant in tumor progression, an important issue is whether a reactive stroma can modulate this process. Using a novel EMT model of colon carcinoma spheroids, we demonstrate that their transforming-growth factor-beta1 (TGF-beta)-induced EMT is accelerated dramatically by the presence of activated macrophages, and we identify tumor necrosis factor-alpha (TNF-alpha) as the critical factor produced by macrophages that accelerates the EMT. A synergy of TNF-alpha and TGF-beta signaling promotes a rapid morphological conversion of the highly organized colonic epithelium to dispersed cells with a mesenchymal phenotype, and this process is dependent on enhanced p38 MAPK activity. Moreover, exposure to TNF-alpha stimulates a rapid burst of ERK activation that results in the autocrine production of this cytokine by the tumor cells themselves. These results establish a novel role for the stroma in influencing EMT in colon carcinoma, and they identify a selective advantage to the stromal presence of infiltrating leukocytes in regulating malignant tumor progression.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12802055&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1091/mbc.E02-09-0583
dc.subjectCell Transformation, Neoplastic
dc.subjectColon
dc.subjectEpithelium
dc.subjectHumans
dc.subjectMesoderm
dc.subjectMitogen-Activated Protein Kinases
dc.subjectOrganoids
dc.subjectTransforming Growth Factor beta
dc.subjectTumor Necrosis Factor-alpha
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleTumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids
dc.typeJournal Article
dc.source.journaltitleMolecular biology of the cell
dc.source.volume14
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/162
dc.identifier.contextkey1633387
html.description.abstract<p>An epithelial-mesenchymal transition (EMT) characterizes the progression of many carcinomas and it is linked to the acquisition of an invasive phenotype. Given that the tumor microenvironment is an active participant in tumor progression, an important issue is whether a reactive stroma can modulate this process. Using a novel EMT model of colon carcinoma spheroids, we demonstrate that their transforming-growth factor-beta1 (TGF-beta)-induced EMT is accelerated dramatically by the presence of activated macrophages, and we identify tumor necrosis factor-alpha (TNF-alpha) as the critical factor produced by macrophages that accelerates the EMT. A synergy of TNF-alpha and TGF-beta signaling promotes a rapid morphological conversion of the highly organized colonic epithelium to dispersed cells with a mesenchymal phenotype, and this process is dependent on enhanced p38 MAPK activity. Moreover, exposure to TNF-alpha stimulates a rapid burst of ERK activation that results in the autocrine production of this cytokine by the tumor cells themselves. These results establish a novel role for the stroma in influencing EMT in colon carcinoma, and they identify a selective advantage to the stromal presence of infiltrating leukocytes in regulating malignant tumor progression.</p>
dc.identifier.submissionpathcancerbiology_pp/162
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages1790-800


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