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Multiple cancer cell types release LIF and Gal3 to hijack neural signals

Qun Xu1, Ying Cao2, Fanni Kong2

  • 1State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China.

Cell Research
|March 12, 2024
PubMed

Insights

Cancer cells hijack the nervous system by releasing leukemia inhibitory factor (LIF) and galectin-3 (Gal3) to promote tumor growth. Blocking these signals or sympathetic actions inhibits cancer progression.

Area of Science:

  • Neuroscience
  • Oncology
  • Immunology

Background:

  • Neural signals impact cancer prognosis, but cancer's modulation of the nervous system is poorly understood.
  • Understanding cancer-cell-driven neural modulation is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate how cancer cells manipulate the nervous system for survival and progression.
  • To identify specific molecular mechanisms by which cancer cells influence neural activity.

Main Methods:

  • Utilized multiple mouse models of peripheral cancers.
  • Performed multi-omic screening to identify key signaling molecules.
  • Investigated the effects of blocking specific cytokines and sympathetic nervous system activity.

Main Results:

  • Identified overlapping brain response patterns in cancer models, particularly in the hypothalamus.
  • Discovered leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as key cancer-derived cytokines triggering brain activation.
  • Observed elevated LIF and Gal3 plasma levels in cancer patients.
  • Demonstrated that blocking LIF/Gal3 signaling or sympathetic actions inhibits tumor growth and restores antitumor immunity.

Conclusions:

  • Cancer cells employ a shared mechanism to hijack the nervous system via LIF and Gal3 signaling.
  • Targeting these cancer-cell-induced neural pathways offers a promising strategy for cancer therapy.

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