Cancer exosomes induce tumor innervation.

Autor:	Madeo M; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Colbert PL; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Vermeer DW; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Lucido CT; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Cain JT; Pediatrics and Rare Diseases Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Vichaya EG; Department of Symptom Research, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 384, Houston, TX, 77030, USA., Grossberg AJ; Department of Symptom Research, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 384, Houston, TX, 77030, USA.; Department of Radiation Medicine, Cancer Early Detection Advanced Research Center, Oregon Health and Science University, 2720 SW Moody Ave KR-CEDR, Portland, OR, 97201, USA., Muirhead D; Sanford Health Pathology Clinic, Sanford Health, 1305 West 18th St, Sioux Falls, SD, 57105, USA., Rickel AP; Biomedical Engineering Program, University of South Dakota, 4800 North Career Ave, Sioux Falls, SD, 57107, USA., Hong Z; Biomedical Engineering Program, University of South Dakota, 4800 North Career Ave, Sioux Falls, SD, 57107, USA., Zhao J; Population Health Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Weimer JM; Pediatrics and Rare Diseases Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA., Spanos WC; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA.; Sanford Ears, Nose and Throat, 1310 West 22nd St, Sioux Falls, SD, 57105, USA., Lee JH; NantKwest, 9920 Jefferson Blvd, Culver City, CA, 90232, USA., Dantzer R; Department of Symptom Research, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 384, Houston, TX, 77030, USA., Vermeer PD; Cancer Biology and Immunotherapies Group, Sanford Research, 2301 East 60th St north, Sioux Falls, SD, 57104, USA. Paola.Vermeer@sanfordhealth.org.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Oct 16; Vol. 9 (1), pp. 4284. Date of Electronic Publication: 2018 Oct 16.
DOI:	10.1038/s41467-018-06640-0
Abstrakt:	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.
Databáze:	MEDLINE
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