Functional Blockade of E-selectin in Tumor-Associated Vessels Enhances Anti-tumor Effect of Doxorubicin in Breast Cancer

Author(s)

Yoshihiro Morita, Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Macall Leslie, Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Hiroyasu Kameyama, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City
Ganesh L. Lokesh, McGovern Medical School, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler
Norihisa Ichimura, Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Rachel Davis, School of Medicine, University of Oklahoma Health Sciences Center
Natalie Hills, School of Medicine, University of Oklahoma Health Sciences Center
Nafis Hasan, Department of Pharmaceutical Sciences, Thomas Jefferson University
Roy Zhang, Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, 940 SL Young Blvd
Yuji Kondo, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation
David G. Gorenstein, AM Biotechnologies, LLC
David E. Volk, McGovern Medical School, Institute of Molecular Medicine, University of Texas Health Science Center at Houston
Inna Chervoneva, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University
Hallgeir Rui, Department of Pathology, Medical College of Wisconsin
Takemi Tanaka, Stephenson Cancer Center, University of Oklahoma Health Sciences Center

Document Type

Article

Abstract

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45 immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45 immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both tumor infiltrating T-lymphocytes and tumor associated-macrophages were skewed towards T2 in DOX-treated residual breast tumors; however, ESTA suppressed these changes. This study suggests that DOX treatment instigates intratumoral infiltration of immune cells through E-selectin, and functional blockade of E-selectin may reduce residual tumor burden as well as metastasis through suppression of T2 shift.

Digital Object Identifier (DOI)

https://doi.org/10.3390/cancers12030725

Publication Info

Cancers, Volume 12, Issue 3, 2020, pages 725-.

Rights

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

APA Citation

Morita, Y., Leslie, M., Kameyama, H., Lokesh, G., Ichimura, N., & Davis, R. et al. (2020). Functional Blockade of E-Selectin in Tumor-Associated Vessels Enhances Anti-Tumor Effect of Doxorubicin in Breast Cancer. Cancers, 12(3), 725. https://doi.org/10.3390/cancers12030725