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Antagonistic Effects of Anti-EMMPRIN Antibody When Combined with Chemotherapy Against Hypovascular Pancreatic Cancers

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Abstract

Purpose

To examine the antagonistic effects of anti-extracellular matrix metalloprotease inducer (anti-EMMPRIN) antibody when combined with chemotherapy using a hypovascular pancreatic tumor model.

Procedures

Severely compromised immunodeficient mice bearing orthotopic MIA PaCa-2 tumors were used (five to six animals per group). Dynamic contrast-enhanced magnetic resonance imaging was used to examine the relationship between tumor vascularity and size. Therapy was initiated when tumors were hypovascular. Treatments included: (1) gemcitabine alone, (2) anti-EMMPRIN antibody alone, and (3) combination, each for 2 weeks. Additionally, another treatment arm included β-lapachone, an NAD(P)H/quinone 1 (NQO1) bioactivated agent. 18F-fluoro-D-glucose-positron emission tomography/computed tomography imaging was used weekly to monitor therapeutic effects.

Results

Gemcitabine or anti-EMMPRIN monotherapy significantly delayed tumor growth, but the combination therapy showed an antagonistic effect. Similarly, tumor growth was significantly suppressed by β-lapachone alone, and additive effects were noted when combined with gemcitabine, but the therapeutic efficacy was reduced when anti-EMMPRIN antibody was added.

Conclusions

Anti-EMMPRIN antibody with chemotherapy in hypovascular tumors results in antagonistic effects.

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Acknowledgments

Authors thank Dr. Lingling Guo for aid in surgically inserting mouse vascular ports and Dr. Eben L. Rosenthal for help in initial study design and consultation. The authors also thank Lee Whitworth and Dr. Jason M. Warram for assistance in growing MIA PaCa-2 cells, animal monitoring, imaging, and drug dosing. We thank Dr. Brenda Yamamoto for analyses of blood cells. This study was supported by a Research Initiative Pilot Award from the Department of Radiology at UAB and NIH grants 2P30CA013148, R01CA142637, P50CA101955, and R01CA102792-13.

Conflict of Interest

Dr. Boothman is a consultant for StemPAR Sciences, Inc.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    Hyunki Kim, Guihua Zhai, Sharon L. Samuel, Amber Martin, Heidi R. Umphrey & Kurt R. Zinn

  2. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    Hyunki Kim

  3. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    Christopher J. Rigell, S. Kyle Lee & Kurt R. Zinn

  4. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    T. Mark Beasley

  5. Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    Donald J. Buchsbaum

  6. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35294-0019, USA

    Hyunki Kim, Heidi R. Umphrey, Cecil R. Stockard & Kurt R. Zinn

  7. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8807, USA

    Long Shan Li & David A. Boothman

  8. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8807, USA

    Long Shan Li & David A. Boothman

  9. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390-8807, USA

    Long Shan Li & David A. Boothman

  10. VH G082, 1720 2nd Avenue South, Birmingham, AL, 35294-0019, USA

    Hyunki Kim

Authors
  1. Hyunki Kim
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  2. Christopher J. Rigell
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  3. Guihua Zhai
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  4. S. Kyle Lee
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  12. David A. Boothman
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Correspondence to Hyunki Kim.

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Kim, H., Rigell, C.J., Zhai, G. et al. Antagonistic Effects of Anti-EMMPRIN Antibody When Combined with Chemotherapy Against Hypovascular Pancreatic Cancers. Mol Imaging Biol 16, 85–94 (2014). https://doi.org/10.1007/s11307-013-0665-4

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  • DOI: https://doi.org/10.1007/s11307-013-0665-4

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