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

Authors

Yoshihiro Morita, University of Oklahoma Health Sciences Center
Macall Leslie, University of Oklahoma Health Sciences Center
Hiroyasu Kameyama, University of Oklahoma Health Sciences Center
Ganesh L R Lokesh, University of Texas Health Science Center at Houston
Norihisa Ichimura, University of Oklahoma Health Sciences Center
Rachel Davis, University of Oklahoma Health Sciences Center
Natalie Hills, University of Oklahoma Health Sciences Center
Nafis Hasan, Thomas Jefferson UniversityFollow
Roy Zhang, University of Oklahoma Health Sciences Center
Yuji Kondo, University of Oklahoma Health Sciences Center
David G Gorenstein, AM Biotechnologies
David E Volk, University of Texas Health Science Center at Houston
Inna Chervoneva, Thomas Jefferson UniversityFollow
Hallgeir Rui, Medical College of Wisconsin
Takemi Tanaka, University of Oklahoma Health Sciences Center

Document Type

Article

Publication Date

3-19-2020

Comments

This article is the author’s final published version in Cancers, Volume 12, Issue 3, March 2020, Article number 725.

The published version is available at https://doi.org/10.3390/cancers12030725. Copyright © Morita et al.

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 TH2 in DOX-treated residual breast tumors; however, ESTA suppressed these changes. This study suggests that DOX treatment instigates de novo 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 TH2 shift.

Recommended Citation

Morita, Yoshihiro; Leslie, Macall; Kameyama, Hiroyasu; Lokesh, Ganesh L R; Ichimura, Norihisa; Davis, Rachel; Hills, Natalie; Hasan, Nafis; Zhang, Roy; Kondo, Yuji; Gorenstein, David G; Volk, David E; Chervoneva, Inna; Rui, Hallgeir; and Tanaka, Takemi, "Functional Blockade of E-Selectin in Tumor-Associated Vessels Enhances Anti-Tumor Effect of Doxorubicin in Breast Cancer" (2020). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 117.
https://jdc.jefferson.edu/petfp/117

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

32204492

Language

English