Related Experiment Video

Updated: Jan 22, 2026

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
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Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer

Man-Tzu Wang1,2, Nicole Fer3, Jacqueline Galeas2

  • 1Tumor Microenvironment Center, UPMC Hillman Cancer Center; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Nature Communications
|July 13, 2019
PubMed

Insights

Leukemia Inhibitory Factor (LIF) is induced by KRAS in pancreatic cancer, driving tumor growth. Blocking LIF with antibodies shows promise in eradicating pancreatic tumors, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • KRAS mutations are prevalent in pancreatic ductal adenocarcinomas (PDAC), correlating with poor prognosis and treatment resistance.
  • Oncogenic KRAS drives tumor progression and therapeutic failure in PDAC.

Purpose of the Study:

  • To investigate the role of Leukemia Inhibitory Factor (LIF) in KRAS-driven pancreatic cancer.
  • To evaluate LIF-neutralizing antibodies as a potential therapeutic strategy for PDAC.

Main Methods:

  • Assessed LIF expression in PDAC induced by oncogenic KRAS.
  • Utilized genetic depletion and neutralizing antibodies to block LIF function in pancreatic xenograft and syngeneic mouse models.
  • Investigated the signaling pathways involved, including Hippo-YAP and STAT signaling.

Main Results:

  • LIF expression is specifically induced by oncogenic KRAS in PDAC.
  • LIF depletion prevented tumor engraftment in xenograft models.
  • LIF-neutralizing antibodies eradicated established PDAC tumors in combination with gemcitabine in a Kras-driven mouse model.
  • LIF, unlike IL-6, inhibits the Hippo-YAP pathway, which is crucial for its function in PDAC cells.

Conclusions:

  • LIF plays a critical role in KRAS-driven pancreatic cancer.
  • Targeting LIF with neutralizing antibodies represents a promising therapeutic approach for PDAC, potentially overcoming resistance to current therapies.

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