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Radiation-induced galectin-1 by endothelial cells: a promising molecular target for preferential drug delivery to the tumor vasculature

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Abstract

The present study reports on a new strategy for selective, radiation therapy-amplified drug delivery using an antiangiogenic 33-a.a., tumor vasculature-targeting ligand, anginex, to improve the therapeutic ratio for strategies developed against solid tumors. Our findings indicate that galectin-1 is (a) one of the major receptors for anginex (b) overexpressed by tumor neovasculature and (c) further specifically upregulated in endothelial cells in response to radiation exposure as low as 0.5 Gy. An investigation of [18]-F-labeled anginex biodistribution in SCK tumors indicates that anginex is an effective targeting molecule for image and radiation-guided therapy of solid tumors. An anginex-conjugated liposome capable of being loaded with drug was shown to selectively target endothelial cells post-radiation. The presence of endothelial cells in a three-dimensional co-culture system with tumor cells developed to study tumor/endothelial cell interactions in vitro led to higher levels of galectin-1 and showed a further increase in expression upon radiation exposure when compared to tumor cell spheroids alone. Similar increase in galectin-1 was observed in tumor tissue originating from the tumor‐endothelial cell spheroids in vivo and radiation exposure further induced galectin-1 in these tumors. The overall results suggest feasibility of using a clinical or subclinical radiation dose to increase expression of the galectin-1 receptor on the tumor microvasculature to promote delivery of therapeutics via the anginex peptide. This approach may reduce systemic toxicity, overcome drug resistance, and improve the therapeutic efficacy of conventional chemo/radiation strategies.

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Acknowledgments

We gratefully acknowledge the research support from National Cancer Institute Grants CA44114 and CA107160 and the Arkansas Biosciences Institute.

Conflict of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY, 40536-0596, USA

    Meenakshi Upreti

  2. Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Azemat Jamshidi-Parsian, Nathan A. Koonce & Robert J. Griffin

  3. Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Scott Apana & Marc Berridge

  4. Department of Physics, Boise State University, Boise, ID, USA

    Daniel A. Fologea

  5. Department of Biological Sciences, University of Arkansas, Fayetteville, Arkansas, USA

    Ralph L. Henry

Authors
  1. Meenakshi Upreti
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  2. Azemat Jamshidi-Parsian
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  3. Scott Apana
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  4. Marc Berridge
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  6. Nathan A. Koonce
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Correspondence to Meenakshi Upreti.

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Upreti, M., Jamshidi-Parsian, A., Apana, S. et al. Radiation-induced galectin-1 by endothelial cells: a promising molecular target for preferential drug delivery to the tumor vasculature. J Mol Med 91, 497–506 (2013). https://doi.org/10.1007/s00109-012-0965-1

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  • DOI: https://doi.org/10.1007/s00109-012-0965-1

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