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TIAM2S Mediates Serotonin Homeostasis and Provokes a Pro-Inflammatory Immune Microenvironment Permissive for

Ya-Ling Chan1, Wei-Chung Lai2, Jia-Shing Chen3

  • 1Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan 701, Taiwan.

Cancers
|July 12, 2020
PubMed

Insights

The short isoform of TIAM2 (TIAM2S) promotes colorectal tumorigenesis by altering immune cell activity and creating a pro-inflammatory environment, linked to serotonin levels.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • The short isoform of TIAM2 (TIAM2S) promotes cancer cell proliferation and invasion.
  • The role of TIAM2S in immune cells concerning tumor development is unexplored.

Purpose of the Study:

  • To investigate the effects of TIAM2S on immune cells and its role in tumor development.
  • To characterize the impact of TIAM2S overexpression on tumorigenesis and the immune microenvironment.

Main Methods:

  • Generated TIAM2S-overexpressing mouse lines (TIAM2S-TG).
  • Assessed tumor development, lymphocytic infiltration, and immune cell populations.
  • Analyzed serotonin levels, Cox2, and chemokine (CXCL13/BCA-1) expression.
  • Investigated IL-23/IL17A expression and tertiary lymphoid organ formation.

Main Results:

  • Aged TIAM2S-TG mice exhibited increased lymphocytic infiltration and tumorigenesis, particularly in the colon.
  • TIAM2S-TG mice showed heightened susceptibility to AOM-induced colon tumor development.
  • TIAM2S overexpression led to T lymphocyte expansion (especially CD8+ T cells) and increased CXCL13/BCA-1.
  • Serotonin and Cox2 were identified as inflammation markers in colonic lesions; tertiary lymphoid organs formed via IL-23/IL17A stimulation.

Conclusions:

  • TIAM2S provokes a pro-inflammatory immune microenvironment conducive to colorectal tumorigenesis.
  • Serotonin-induced immunomodulatory effects of TIAM2S play a key role in this process.
  • TIAM2S influences immune cell recruitment and activation, fostering conditions that promote tumor growth.
Keywords:
T lymphocyteT-cell lymphoma invasion and metastasis 2chronic inflammationinflammatory bowel diseaseserotonin

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