TY - JOUR
T1 - Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells
AU - Peak, Taylor C.
AU - Praharaj, Prakash P.
AU - Panigrahi, Gati K.
AU - Doyle, Michael
AU - Su, Yixin
AU - Schlaepfer, Isabel R.
AU - Singh, Ravi
AU - Vander Griend, Donald J.
AU - Alickson, Julie
AU - Hemal, Ashok
AU - Atala, Anthony
AU - Deep, Gagan
N1 - Funding Information:
We acknowledge grant support from the National Cancer Institute (R21 CA199628 to GD) and NCI K01-CA168934 (to IRS). We also acknowledge the support of the Wake Forest Baptist Comprehensive cancer center Proteomics and Metabolomics shared resource, supported by NCI's Cancer Center Support grant (P30CA012197, PI: Dr. Boris Pasche).
Funding Information:
We acknowledge grant support from the National Cancer Institute ( R21 CA199628 to GD) and NCI K01-CA168934 (to IRS). We also acknowledge the support of the Wake Forest Baptist Comprehensive cancer center Proteomics and Metabolomics shared resource, supported by NCI's Cancer Center Support grant ( P30CA012197 , PI: Dr. Boris Pasche).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/5/23
Y1 - 2018/5/23
N2 - The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSCExo) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5.23 × 1010±1.99 × 109 per ml) secreted by PLSC. PLSCExo treatment strongly inhibited the viability of enzalutamide-sensitive and -resistant PCa cell lines (C4-2B, CWR-R1, and LNCaP cells). Interestingly, PLSCExo treatment had no effect on the viability of a non-neoplastic human prostate cell line (PREC-1). Mass spectrometry (MS) analyses showed that PLSCExo are loaded with 241 proteins and mainly with saturated fatty acids. Further, Ingenuity Pathway Analysis analyses of proteins loaded in PLSCExo suggested the role of retinoic acid receptor/liver x receptor pathways in their biological effects. Together, these results suggest the novel selective anti-cancer effects of PLSCExo against aggressive PCa cells.
AB - The current paradigm in the development of new cancer therapies is the ability to target tumor cells while avoiding harm to noncancerous cells. Furthermore, there is a need to develop novel therapeutic options against drug-resistant cancer cells. Herein, we characterized the placental-derived stem cell (PLSC) exosomes (PLSCExo) and evaluated their anti-cancer efficacy in prostate cancer (PCa) cell lines. Nanoparticle tracking analyses revealed the size distribution (average size 131.4 ± 0.9 nm) and concentration of exosomes (5.23 × 1010±1.99 × 109 per ml) secreted by PLSC. PLSCExo treatment strongly inhibited the viability of enzalutamide-sensitive and -resistant PCa cell lines (C4-2B, CWR-R1, and LNCaP cells). Interestingly, PLSCExo treatment had no effect on the viability of a non-neoplastic human prostate cell line (PREC-1). Mass spectrometry (MS) analyses showed that PLSCExo are loaded with 241 proteins and mainly with saturated fatty acids. Further, Ingenuity Pathway Analysis analyses of proteins loaded in PLSCExo suggested the role of retinoic acid receptor/liver x receptor pathways in their biological effects. Together, these results suggest the novel selective anti-cancer effects of PLSCExo against aggressive PCa cells.
KW - Exosomes
KW - Mass spectrometry
KW - Placental stem cells
KW - Prostate cancer
KW - Retinoic acid receptor
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U2 - 10.1016/j.bbrc.2018.04.038
DO - 10.1016/j.bbrc.2018.04.038
M3 - Article
C2 - 29627574
AN - SCOPUS:85045116986
SN - 0006-291X
VL - 499
SP - 1004
EP - 1010
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -