Pulmonary Carcinoid Surface Receptor Modulation Using Histone Deacetylase Inhibitors

Date

2019-06-03

Authors

Guenter, Rachael E.
Aweda, Tolulope
Carmona Matos, Danilea M.
Whitt, Jason
Chang, Alexander W.
Cheng, Eric Y.
Liu, X. Margaret
Chen, Herbert
Lapi, Suzanne E.
Jaskula-Sztul, Renata

ORCID

0000-0001-9336-2593 (Cheng, Eric Yi-Qiang)

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI

Abstract

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 [(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.

Description

Citation

Guenter, 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

Rights

© 2019 by the authors.

License

Attribution 4.0 International (CC BY 4.0)