Open Access

Tumor‑derived exosomes educate fibroblasts to promote salivary adenoid cystic carcinoma metastasis via NGF‑NTRK1 pathway

  • Authors:
    • Zhengli Xu
    • Xing Zheng
    • Jianming Zheng
  • View Affiliations

  • Published online on: August 14, 2019     https://doi.org/10.3892/ol.2019.10740
  • Pages: 4082-4091
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Salivary adenoid cystic carcinoma (SACC) is a rare head and neck malignancy characterized by unpredictable expansion, considerable perineural invasion and high risk of metastasis; however, the underlying mechanism of SACC progression remains unclear. Cancer‑associated fibroblasts localized within the tumor microenvironment may promote cancer malignant transformation by enhancing tumor growth, blood vessel formation, inflammation development and metastasis occurrence. Small extracellular vesicles, including exosomes, are mediators of intercellular communication and can influence major tumor‑associated pathways. The present study aimed to explore the exosome‑mediated communication between SACC cells and fibroblasts. The results from confocal microscopy demonstrated that exosomes derived from the human cell line SACC‑83 were internalized by the human periodontal ligament fibroblast (HPLF) cells. Following exosome internalization, HPLF cells appeared to enhance SACC‑83 cell metastasis and were educated toward a protumorigenesis phenotype according to transcriptome RNA sequencing and reverse transcription‑quantitative polymerase chain reaction analysis. This phenomenon included exosome‑mediated stimulation of proinflammatory cytokines and nerve growth factor (NGF) secretion. Furthermore, NGF blockage reduced the enhanced SACC‑83 cell invasion stimulated by the supernatant isolated from exosome‑educated HPLF cells. In addition, the results reported that neurotrophic receptor tyrosine kinase 1 (NTRK1), which is the high‑affinity NGF receptor, was significantly upregulated in human SACC‑83 cells. These results demonstrated that SACC‑83 cell‑derived exosomes educated HPLF cells toward the protumorigenic phenotype via the NGF‑NTRK1 pathway, which suggested that this type of exosomes may be used as a potential therapeutic target for SACC.

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October 2019
Volume 18 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
APA
Xu, Z., Zheng, X., & Zheng, J. (2019). Tumor‑derived exosomes educate fibroblasts to promote salivary adenoid cystic carcinoma metastasis via NGF‑NTRK1 pathway. Oncology Letters, 18, 4082-4091. https://doi.org/10.3892/ol.2019.10740
MLA
Xu, Z., Zheng, X., Zheng, J."Tumor‑derived exosomes educate fibroblasts to promote salivary adenoid cystic carcinoma metastasis via NGF‑NTRK1 pathway". Oncology Letters 18.4 (2019): 4082-4091.
Chicago
Xu, Z., Zheng, X., Zheng, J."Tumor‑derived exosomes educate fibroblasts to promote salivary adenoid cystic carcinoma metastasis via NGF‑NTRK1 pathway". Oncology Letters 18, no. 4 (2019): 4082-4091. https://doi.org/10.3892/ol.2019.10740