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MUC5AC protects pancreatic cancer cells from TRAIL-induced death pathways

Hirotaka Hoshi1, Tetsuji Sawada, Motoyuki Uchida

  • 1Biomedical Research Laboratories, Kureha Corporation, Shinjuku-ku, Tokyo 169-8503, Japan.

International Journal of Oncology
|January 8, 2013
PubMed

Insights

Mucin 5AC (MUC5AC) knockdown suppresses pancreatic cancer growth by enabling neutrophil-mediated tumor cell apoptosis. MUC5AC inhibits tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Previous studies showed MUC5AC siRNA suppressed in vivo tumor growth and metastasis without affecting in vitro cell characteristics.
  • The specific host immune cells and mechanisms responsible for MUC5AC's in vivo effects remained unclear.

Purpose of the Study:

  • To identify the host immune cells mediating the antitumor effects of MUC5AC knockdown.
  • To elucidate the mechanism by which MUC5AC influences tumor cell susceptibility to immune attack, specifically TRAIL-induced apoptosis.

Main Methods:

  • Utilized immunocyte-depleted animal models (nude mice) to assess tumor growth after MUC5AC knockdown.
  • Administered anti-Gr-1 mAb to deplete neutrophils and observed effects on SW1990/si-MUC5AC tumor growth.
  • Investigated the impact of MUC5AC on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by measuring active caspase 3 expression.

Main Results:

  • Depletion of neutrophils using anti-Gr-1 mAb restored tumor growth of SW1990/si-MUC5AC cells, indicating neutrophils mediate the antitumor effect.
  • MUC5AC knockdown cells (SW1990/si-MUC5AC) exhibited significantly increased active caspase 3 expression upon TRAIL treatment compared to control cells.
  • MUC5AC appears to protect tumor cells from TRAIL-induced apoptosis, suggesting a mechanism for immune evasion.

Conclusions:

  • Neutrophils are key host immune cells suppressing MUC5AC-expressing pancreatic tumor growth.
  • MUC5AC inhibits neutrophil-mediated antitumor activity by preventing TRAIL-induced apoptosis in pancreatic cancer cells.
  • MUC5AC may serve as a diagnostic and prognostic biomarker in human pancreatic cancer.

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