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Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung
Hironori Satoh1, Takashi Moriguchi, Keiko Taguchi
1Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
Carcinogenesis
|June 2, 2010
Summary
The Nrf2 pathway protects against cancer metastasis by maintaining immune system redox balance. Nrf2 deficiency increases lung metastasis and myeloid-derived suppressor cells (MDSCs), impairing T-cell immunity.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Cancer Research
Background:
- The Nrf2 transcription factor is vital for cellular defense against carcinogens.
- The role of Nrf2 in cancer metastasis is not well understood.
Purpose of the Study:
- To investigate the role of Nrf2 in host susceptibility to cancer metastasis.
- To elucidate the mechanisms by which Nrf2 influences metastasis and immune cell function.
Main Methods:
- Nrf2-deficient and wild-type mice were used to study pulmonary metastasis of Lewis lung carcinoma cells.
- Bone marrow transplantation experiments were performed.
- Levels of reactive oxygen species (ROS) and immune cell populations (MDSCs, CD8+ T-cells) were analyzed.
Main Results:
- Nrf2-deficient mice showed significantly increased pulmonary metastasis compared to wild-type mice.
- Increased inflammatory cells, including MDSCs with elevated ROS, were found in Nrf2-deficient mice.
- Nrf2 deficiency impaired CD8+ T-cell immunity and altered hematopoietic/immune system function.
Conclusions:
- Nrf2 plays a critical role in preventing cancer metastasis.
- Nrf2 preserves redox balance in the immune system, suppressing MDSC-mediated immunosuppression and promoting anti-tumor immunity.
