The release of tryptase from mast cells promote tumor cell metastasis via exosomes

BMC Cancer. 2019 Oct 29;19(1):1015. doi: 10.1186/s12885-019-6203-2.

Abstract

Background: Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown.

Method: Exosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting.

Results: In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway.

Conclusions: Our results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.

Keywords: Angiogenesis; Exosomes; Lung cancer; Mast cell; Tryptase.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / secondary*
  • Bone Marrow Cells / metabolism
  • Cell Degranulation
  • Cell Movement
  • Cell Proliferation
  • Cytokines / metabolism
  • Exosomes / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Janus Kinases / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Mast Cells / metabolism*
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Stem Cell Factor / metabolism
  • Tryptases / metabolism*

Substances

  • Cytokines
  • KITLG protein, human
  • STAT Transcription Factors
  • Stem Cell Factor
  • Janus Kinases
  • Tryptases