Pulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors

dc.creatorGuenter, Rachael E.
dc.creatorAweda, Tolulope
dc.creatorCarmona Matos, Danilea M.
dc.creatorWhitt, Jason
dc.creatorChang, Alexander W.
dc.creatorCheng, Eric Y.
dc.creatorLiu, X. Margaret
dc.creatorChen, Herbert
dc.creatorLapi, Suzanne E.
dc.creatorJaskula-Sztul, Renata
dc.creator.orcid0000-0001-9336-2593 (Cheng, Eric Yi-Qiang)
dc.date.accessioned2022-08-25T19:58:38Z
dc.date.available2022-08-25T19:58:38Z
dc.date.issued2019-06-03
dc.description.abstractPulmonary carcinoids are a type of neuroendocrine tumor (NET) accounting for 1-2% of lung cancer cases. Currently, Positron Emission Tomography (PET)/CT based on the radiolabeled sugar analogue [(18)F]-FDG is used to diagnose and stage pulmonary carcinoids, but is suboptimal due to low metabolic activity in these tumors. A new technique for pulmonary carcinoid imaging, using PET/CT with radiolabeled somatostatin analogs that specifically target somatostatin receptor subtype 2 (SSTR2), is becoming more standard, as many tumors overexpress SSTR2. However, pulmonary carcinoid patients with diminished SSTR2 expression are not eligible for this imaging or any type of SSTR2-specific treatment. We have found that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 in pulmonary carcinoid cell lines. In this study, we used a non-cytotoxic dose of HDAC inhibitors to induce pulmonary carcinoid SSTR2 expression in which we confirmed in vitro and in vivo. A non-cytotoxic dose of the HDAC inhibitors: thailandepsin A (TDP-A), romidepsin (FK228), suberoylanilide hydroxamic acid (SAHA), AB3, and valproic acid (VPA) were administered to promote SSTR2 expression in pulmonary carcinoid cell lines and xenografts. This SSTR2 upregulation technique using HDAC inhibitors could enhance radiolabeled somatostatin analog-based imaging and the development of potential targeted treatments for pulmonary carcinoid patients with marginal or diminished SSTR2 expression.
dc.description.sponsorshipResearch reported in this publication was supported by the National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The animal imaging studies were supported through P30CA013148, the UAB Comprehensive Cancer Center's Preclinical Imaging Shared Facility.
dc.identifier.citationGuenter, R. E., Aweda, T., Carmona Matos, D. M., Whitt, J., Chang, A. W., Cheng, E. Y., Liu, X. M., Chen, H., Lapi, S. E., & Jaskula-Sztul, R. (2019). Pulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors. Cancers, 11(6), 767. https://doi.org/10.3390/cancers11060767
dc.identifier.issn2072-6694
dc.identifier.issue6
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31661
dc.identifier.volume11
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cancers11060767
dc.rights.holder© 2019 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCancers (Basel)
dc.subjecthistone deacetylase inhibitor
dc.subjectneuroendocrine cancer
dc.subjectpulmonary carcinoid
dc.subjectsomatostatin receptor
dc.titlePulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors
dc.typeArticle
dc.type.materialtext

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