TY - JOUR
T1 - Pulmonary carcinoid surface receptor modulation using histone deacetylase inhibitors
AU - Guenter, Rachael E.
AU - Aweda, Tolulope
AU - Matos, Danilea M.Carmona
AU - Whitt, Jason
AU - Chang, Alexander W.
AU - Cheng, Eric Y.
AU - Liu, X. Margaret
AU - Chen, Herbert
AU - Lapi, Suzanne E.
AU - Jaskula-Sztul, Renata
N1 - Funding Information:
Grant-In-Aid for Scientific Research from the Ministry of Education of Japan to H.H., H.U. and K.K.
Funding Information:
Funding: Research 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.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/6
Y1 - 2019/6
N2 - Pulmonary 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 [18F]-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.
AB - Pulmonary 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 [18F]-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.
KW - Histone deacetylase inhibitor
KW - Neuroendocrine cancer
KW - Pulmonary carcinoid
KW - Somatostatin receptor
UR - http://www.scopus.com/inward/record.url?scp=85070775605&partnerID=8YFLogxK
U2 - 10.3390/cancers11060767
DO - 10.3390/cancers11060767
M3 - Article
AN - SCOPUS:85070775605
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 6
M1 - 767
ER -