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Identifying the murine mammary cell target of metformin exposure

Mona Shehata1, Hyeyeon Kim1, Ravi Vellanki1

  • 1Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7 Canada.

Communications Biology
|May 25, 2019
PubMed

Insights

Metformin, an anti-diabetic drug, impacts normal breast tissue by targeting hormone receptor positive (HR+) luminal cells. This study reveals specific cellular changes, suggesting potential for targeted cancer prevention strategies.

Area of Science:

  • Oncology
  • Endocrinology
  • Cell Biology

Background:

  • Breast cancer heterogeneity poses therapeutic challenges.
  • Metformin exhibits anti-cancer properties in studies.
  • The effect of metformin on normal breast tissue is not well understood.

Purpose of the Study:

  • To investigate the impact of metformin on normal adult murine mammary gland cells.
  • To identify specific cell types targeted by metformin in the mammary gland.
  • To explore the potential of metformin for breast cancer prevention.

Main Methods:

  • Administration of metformin at a clinically relevant dose to murine models.
  • Analysis of cellular changes in different mammary gland cell populations.
  • Assessment of cell number, progenitor capacity, DNA damage, oxygen consumption, and cell cycle length.

Main Results:

  • Metformin significantly affects hormone receptor positive (HR+) luminal cells in the normal mammary gland.
  • Metformin reduces cell number, progenitor capacity, and DNA damage in HR+ luminal cells.
  • HR+ luminal cells exhibit reduced oxygen consumption and increased cell cycle length, with lower mitochondrial respiration and oxidative stress handling capacity.

Conclusions:

  • HR+ luminal cells are a primary target of metformin in the normal mammary gland.
  • The observed effects suggest intrinsic susceptibility of HR+ luminal cells to metformin.
  • Identifying this target could refine patient selection for metformin-based cancer prevention or therapy.
Keywords:
Breast cancerDisease modelTarget validation

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