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  11. Aqp5 Enriches For Stem Cells And Cancer Origins In The Distal Stomach.

AQP5 enriches for stem cells and cancer origins in the distal stomach.

Si Hui Tan1, Yada Swathi1, Shawna Tan1

  • 1A*STAR Institute of Medical Biology, Singapore, Singapore.

Nature
|February 7, 2020

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View abstract on PubMed

Summary
This summary is machine-generated.

Researchers identified Aquaporin 5 (AQP5) as a marker for adult pyloric stem cells in mice and humans. This discovery aids in understanding gastric cancer origins and developing regenerative medicine for stomach stem cells.

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Area of Science:

  • Gastroenterology and Oncology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • LGR5 identifies mouse pyloric stem cells, but human equivalents are unknown due to lack of specific markers.
  • LGR5+ intestinal stem cells drive WNT-driven cancer in mice; their role in gastric cancer is unclear.
  • WNT pathway dysregulation is common in human gastric cancer.

Purpose of the Study:

  • To identify and validate a surface marker for human and mouse adult pyloric stem cells.
  • To investigate the role of identified stem cells in WNT-driven gastric cancer.
  • To establish new models for studying gastric cancer initiation and human stomach stem cells.

Main Methods:

  • Comparative profiling of LGR5+ stem cell populations across the mouse gastrointestinal tract.
  • Functional validation of Aquaporin 5 (AQP5) as a stem cell marker.
  • Generation of Aqp5-creERT2 mouse models for in vivo cancer studies.
  • In vitro organoid culture to assess tumor-initiating capacity of AQP5+ cells.

Main Results:

  • AQP5 was identified as a marker enriching for mouse and human adult pyloric stem cells.
  • AQP5+ stem cells fuel WNT-driven, invasive gastric cancer in vivo.
  • Tumor-resident AQP5+ cells demonstrated selective organoid initiation, indicating cancer stem cell potential.
  • AQP5 expression and localization are altered in human gastric cancer subtypes and metastases.

Conclusions:

  • AQP5 is a validated marker for adult pyloric stem cells in mice and humans.
  • Pyloric stem cells marked by AQP5 are a source of WNT-driven gastric cancer.
  • The identified markers and models are crucial for studying gastric cancer development and human stomach stem cell biology.
  • This research paves the way for regenerative medicine applications using human stomach stem cells.