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dc.contributor.authorChen, Ya-Wen
dc.contributor.authorBoyartchuk, Victor L.
dc.contributor.authorLewis, Brian C.
dc.date2022-08-11T08:09:39.000
dc.date.accessioned2022-08-23T16:39:04Z
dc.date.available2022-08-23T16:39:04Z
dc.date.issued2009-09-03
dc.date.submitted2010-04-06
dc.identifier.citation<p>Neoplasia. 2009 Sep;11(9):835-45.</p>
dc.identifier.issn1476-5586 (Linking)
dc.identifier.pmid19724677
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39389
dc.description.abstractIntrahepatic and extrahepatic metastases are common findings in hepatocellular carcinoma (HCC). Insulin-like growth factor 2 (IGF2) expression is frequently induced in HCC, and serum IGF2 levels correlate with the presence of extrahepatic metastases. Yet, the role of IGF-induced signaling in the dissemination of HCC remains unclear. We have previously observed elevated IGF2 levels in tumors with metastatic potential in an HCC mouse model. Here, we demonstrate that inhibition of IGF2, or its receptor IGF1R, impairs the migration and invasion activities of murine HCC cells. Furthermore, inhibition of IGF1R also impairs the ability of HCC cells to colonize the lungs after introduction into the circulation through the tail vein but does not impair subcutaneous tumor growth. Collectively, these findings suggest that IGF1R-mediated signaling plays a causative role in tumor dissemination but is not required for tumor growth per se. Although previous studies indicate that IGF ligands can signal through IGF1R/insulin receptor (IR) heterodimers, and IR-A homodimers, we demonstrate that the IR is not required for invasion and metastasis by HCC cells. Finally, we identify matrix metalloproteinase 2 as a mediator of the invasive phenotype downstream of IGF1R-induced signaling. Thus, our studies demonstrate the importance of IGF2-induced signaling in the dissemination of HCC cells.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=19724677&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735682/
dc.subjectAnimals
dc.subjectBlotting, Western
dc.subjectCarcinoma, Hepatocellular
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectImmunoblotting
dc.subjectInsulin Receptor Substrate Proteins
dc.subjectInsulin-Like Growth Factor II
dc.subjectLiver Neoplasms
dc.subjectMale
dc.subjectMatrix Metalloproteinase 3
dc.subjectMatrix Metalloproteinase 9
dc.subjectMice
dc.subjectMice, Nude
dc.subjectNeoplasm Invasiveness
dc.subjectPhenotype
dc.subjectRNA, Messenger
dc.subjectReceptor, IGF Type 1
dc.subjectReceptor, Insulin
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subject*Signal Transduction
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDifferential roles of insulin-like growth factor receptor- and insulin receptor-mediated signaling in the phenotypes of hepatocellular carcinoma cells
dc.typeJournal Article
dc.source.journaltitleNeoplasia (New York, N.Y.)
dc.source.volume11
dc.source.issue9
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2185
dc.identifier.contextkey1262965
html.description.abstract<p>Intrahepatic and extrahepatic metastases are common findings in hepatocellular carcinoma (HCC). Insulin-like growth factor 2 (IGF2) expression is frequently induced in HCC, and serum IGF2 levels correlate with the presence of extrahepatic metastases. Yet, the role of IGF-induced signaling in the dissemination of HCC remains unclear. We have previously observed elevated IGF2 levels in tumors with metastatic potential in an HCC mouse model. Here, we demonstrate that inhibition of IGF2, or its receptor IGF1R, impairs the migration and invasion activities of murine HCC cells. Furthermore, inhibition of IGF1R also impairs the ability of HCC cells to colonize the lungs after introduction into the circulation through the tail vein but does not impair subcutaneous tumor growth. Collectively, these findings suggest that IGF1R-mediated signaling plays a causative role in tumor dissemination but is not required for tumor growth per se. Although previous studies indicate that IGF ligands can signal through IGF1R/insulin receptor (IR) heterodimers, and IR-A homodimers, we demonstrate that the IR is not required for invasion and metastasis by HCC cells. Finally, we identify matrix metalloproteinase 2 as a mediator of the invasive phenotype downstream of IGF1R-induced signaling. Thus, our studies demonstrate the importance of IGF2-induced signaling in the dissemination of HCC cells.</p>
dc.identifier.submissionpathoapubs/2185
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages835-45


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