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dc.contributor.authorDuquette, Marken_US
dc.contributor.authorSadow, Peter M.en_US
dc.contributor.authorLawler, Jacken_US
dc.contributor.authorNucera, Carmeloen_US
dc.date.accessioned2014-03-11T10:17:54Z
dc.date.issued2013en_US
dc.identifier.citationDuquette, Mark, Peter M. Sadow, Jack Lawler, and Carmelo Nucera. 2013. “Thrombospondin-1 Silencing Down-Regulates Integrin Expression Levels in Human Anaplastic Thyroid Cancer Cells with BRAFV600E: New Insights in the Host Tissue Adaptation and Homeostasis of Tumor Microenvironment.” Frontiers in Endocrinology 4 (1): 189. doi:10.3389/fendo.2013.00189. http://dx.doi.org/10.3389/fendo.2013.00189.en
dc.identifier.issn1664-2392en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879437
dc.description.abstractBackground and Rationale: Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer progression by regulating cell stromal cross-talk in the tumor microenvironment. Goals: Our goal was to understand whether TSP-1 could affect protein levels of its integrin receptors (e.g., ITGα3, α6, and β1) and cell morphology in BRAFV600E-ATC cells in vitro and in vivo. Experimental Design: Anaplastic thyroid cancer-derived cell cultures and western blotting were used to assess integrin protein expression upon TSP-1 silencing. Immunohistochemistry was performed on orthotopic primary human ATC and metastatic ATC in lung tissue to compare TSP-1 and integrin protein expression levels. Results:: TSP-1 knock-down down-regulates ITGα3, α6, and β1 in BRAFV600E-human ATC cells. BRAFV600E-ATC cells with TSP-1 knock-down were rounded compared to control cells, which displayed a spread morphology. TSP-1 knock-down also reduced TSP-1, ITGα3, α6, and β1 protein expression levels in vivo in the ATC microenvironment, which is enriched in stromal and inflammatory cells. Conclusion:: TSP-1 silencing causes changes in ITG levels and ATC cell morphology. The assessment of TSP-1 and ITG levels might contribute to earlier metastatic potential of BRAFV600E-positive aggressive thyroid cancers, and allow improved patient selection for clinical trials.en
dc.language.isoen_USen
dc.publisherFrontiers Media S.A.en
dc.relation.isversionofdoi:10.3389/fendo.2013.00189en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845490/pdf/en
dash.licenseLAAen_US
dc.subjectBRAFen
dc.subjectintegrinsen
dc.subjectthyroid canceren
dc.subjectmicroenvironmenten
dc.subjectextracellular matrixen
dc.subjectTSP-1en
dc.titleThrombospondin-1 Silencing Down-Regulates Integrin Expression Levels in Human Anaplastic Thyroid Cancer Cells with BRAFV600E: New Insights in the Host Tissue Adaptation and Homeostasis of Tumor Microenvironmenten
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalFrontiers in Endocrinologyen
dash.depositing.authorSadow, Peter M.en_US
dc.date.available2014-03-11T10:17:54Z
dc.identifier.doi10.3389/fendo.2013.00189*
dash.contributor.affiliatedLawler, Jack
dash.contributor.affiliatedNucera, Carmelo
dash.contributor.affiliatedSadow, Peter


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