Neutrophil Elastase Facilitates Tumor Cell Intravasation and Early Metastatic Events

Elena Deryugina, Alexia Carré, Veronica Ardi, Tomoki Muramatsu, Jonas Schmidt, Christine Pham, James P. Quigley

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Functional roles of neutrophil elastase (NE) have not been examined in distinct steps of the metastatic cascade. NE, delivered to primary tumors as a purified enzyme or within intact neutrophils or neutrophil granule content, enhanced human tumor cell intravasation and subsequent dissemination via NE-mediated formation of dilated intratumoral vasculature. These effects depended on picomole range of NE activity, sensitive to its natural inhibitor, α1PI. In Elane-negative mice, the lack of NE decreased lung retention of human tumor cells in experimental metastasis. Furthermore, NE was essential for spontaneous metastasis of murine carcinoma cells in a syngeneic orthotopic model of oral cancer. NE also induced tumor cell survival and migration via Src/PI3K-dependent activation of Akt signaling, vital for tumor cell dissemination in vivo. Together, our findings implicate NE, a potent host enzyme specific for first-responding innate immune cells, as directly involved in early metastatic events and a potential target for therapeutic intervention.

Original languageEnglish
Article number101799
JournaliScience
Volume23
Issue number12
DOIs
StatePublished - Dec 18 2020

Keywords

  • Cancer
  • Cell Biology

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