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Int. J. Mol. Sci. 2017, 18(12), 2671; https://doi.org/10.3390/ijms18122671

Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models

1
Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2
National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, USA
*
Authors to whom correspondence should be addressed.
Received: 6 November 2017 / Revised: 1 December 2017 / Accepted: 5 December 2017 / Published: 9 December 2017
(This article belongs to the Special Issue Galectins in Cancer and Translational Medicine)
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Abstract

Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO2) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1—e.g., by OTX008—may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care. View Full-Text
Keywords: galectin-1 inhibitor; OTX008; Avastin; Anginex; hypoxia; pimonidazole; vessel normalization galectin-1 inhibitor; OTX008; Avastin; Anginex; hypoxia; pimonidazole; vessel normalization
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Koonce, N.A.; Griffin, R.J.; Dings, R.P.M. Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models. Int. J. Mol. Sci. 2017, 18, 2671.

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