TY - JOUR
T1 - Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors
AU - Madhankumar, A. B.
AU - Mrowczynski, Oliver D.
AU - Slagle-Webb, Becky
AU - Ravi, Vagisha
AU - Bourcier, Alexandre J.
AU - Payne, Russell
AU - Harbaugh, Kimberly S.
AU - Rizk, Elias
AU - Connor, James R.
N1 - Funding Information:
This project got funding support from Tara Leah Witmer Memorial Foundation, PA. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. Abhijit Guha, University of Toronto for providing us with ST88-14 MPNST cells for our experiments and Dr. Daniel Scoles, University of Utah for providing STS26T cells, Wade Edris in the Penn State Hershey Confocal microscopy core facility for his assistance in imaging and Anne Park for her assistance in some immunoblot experiments during her Medical Student Research project at Penn State Hershey Medical Center. We like to acknowledge the funding support by Tara Leah Witmer Memorial Foundation, PA for this research.
Publisher Copyright:
© 2018 Madhankumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/1
Y1 - 2018/1
N2 - Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
AB - Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
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U2 - 10.1371/journal.pone.0181529
DO - 10.1371/journal.pone.0181529
M3 - Article
C2 - 29304038
AN - SCOPUS:85040180084
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 1
M1 - e0181529
ER -