Cancer exosomes induce tumor innervation

Marianna Madeo, Paul L. Colbert, Daniel W. Vermeer, Christopher T. Lucido, Jacob T. Cain, Elisabeth G. Vichaya, Aaron Grossberg, Desi Rae Muirhead, Alex P. Rickel, Zhongkui Hong, Jing Zhao, Jill M. Weimer, William C. Spanos, John H. Lee, Robert Dantzer, Paola D. Vermeer

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.

Original languageEnglish (US)
Article number4284
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Exosomes
Tumors
tumors
cancer
Neoplasms
nerves
PC12 Cells
metastasis
cells
Neurites
mice

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Madeo, M., Colbert, P. L., Vermeer, D. W., Lucido, C. T., Cain, J. T., Vichaya, E. G., ... Vermeer, P. D. (2018). Cancer exosomes induce tumor innervation. Nature communications, 9(1), [4284]. https://doi.org/10.1038/s41467-018-06640-0

Cancer exosomes induce tumor innervation. / Madeo, Marianna; Colbert, Paul L.; Vermeer, Daniel W.; Lucido, Christopher T.; Cain, Jacob T.; Vichaya, Elisabeth G.; Grossberg, Aaron; Muirhead, Desi Rae; Rickel, Alex P.; Hong, Zhongkui; Zhao, Jing; Weimer, Jill M.; Spanos, William C.; Lee, John H.; Dantzer, Robert; Vermeer, Paola D.

In: Nature communications, Vol. 9, No. 1, 4284, 01.12.2018.

Research output: Contribution to journalArticle

Madeo, M, Colbert, PL, Vermeer, DW, Lucido, CT, Cain, JT, Vichaya, EG, Grossberg, A, Muirhead, DR, Rickel, AP, Hong, Z, Zhao, J, Weimer, JM, Spanos, WC, Lee, JH, Dantzer, R & Vermeer, PD 2018, 'Cancer exosomes induce tumor innervation', Nature communications, vol. 9, no. 1, 4284. https://doi.org/10.1038/s41467-018-06640-0
Madeo M, Colbert PL, Vermeer DW, Lucido CT, Cain JT, Vichaya EG et al. Cancer exosomes induce tumor innervation. Nature communications. 2018 Dec 1;9(1). 4284. https://doi.org/10.1038/s41467-018-06640-0
Madeo, Marianna ; Colbert, Paul L. ; Vermeer, Daniel W. ; Lucido, Christopher T. ; Cain, Jacob T. ; Vichaya, Elisabeth G. ; Grossberg, Aaron ; Muirhead, Desi Rae ; Rickel, Alex P. ; Hong, Zhongkui ; Zhao, Jing ; Weimer, Jill M. ; Spanos, William C. ; Lee, John H. ; Dantzer, Robert ; Vermeer, Paola D. / Cancer exosomes induce tumor innervation. In: Nature communications. 2018 ; Vol. 9, No. 1.
@article{cca8cf88734e4c23b2a27b7fd4be9102,
title = "Cancer exosomes induce tumor innervation",
abstract = "Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.",
author = "Marianna Madeo and Colbert, {Paul L.} and Vermeer, {Daniel W.} and Lucido, {Christopher T.} and Cain, {Jacob T.} and Vichaya, {Elisabeth G.} and Aaron Grossberg and Muirhead, {Desi Rae} and Rickel, {Alex P.} and Zhongkui Hong and Jing Zhao and Weimer, {Jill M.} and Spanos, {William C.} and Lee, {John H.} and Robert Dantzer and Vermeer, {Paola D.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41467-018-06640-0",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Cancer exosomes induce tumor innervation

AU - Madeo, Marianna

AU - Colbert, Paul L.

AU - Vermeer, Daniel W.

AU - Lucido, Christopher T.

AU - Cain, Jacob T.

AU - Vichaya, Elisabeth G.

AU - Grossberg, Aaron

AU - Muirhead, Desi Rae

AU - Rickel, Alex P.

AU - Hong, Zhongkui

AU - Zhao, Jing

AU - Weimer, Jill M.

AU - Spanos, William C.

AU - Lee, John H.

AU - Dantzer, Robert

AU - Vermeer, Paola D.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.

AB - Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.

UR - http://www.scopus.com/inward/record.url?scp=85055072132&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055072132&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-06640-0

DO - 10.1038/s41467-018-06640-0

M3 - Article

C2 - 30327461

AN - SCOPUS:85055072132

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4284

ER -