ReferenceID 3899
Tamoxifen, flaxseed, and the lignan enterolactone increase stroma- and cancer cell-derived IL-1Ra and decrease tumor angiogenesis in estrogen-dependent breast cancer
Cancer Res
The proinflammatory cytokines IL-1α and IL-1β promote tumor angiogenesis that might be counteracted by the IL-1 receptor antagonist (IL-1Ra), anakinra, a clinically approved agent. A diet with high amounts of phytoestrog
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3899
- Evidence Id
- 20489
- Core Evidence Id
- 20489
- Source Reference Id
- 1080
- Herb2 Reference Id
- HBREF001816
- Subject Paper Key
- HBIN025188_21097717
- Pubmed Id
- 21097717
- Doi
- 10.1158/0008-5472.CAN-10-2289
- Paper Title
- Tamoxifen, flaxseed, and the lignan enterolactone increase stroma- and cancer cell-derived IL-1Ra and decrease tumor angiogenesis in estrogen-dependent breast cancer
- Paper Abstract
- The proinflammatory cytokines IL-1α and IL-1β promote tumor angiogenesis that might be counteracted by the IL-1 receptor antagonist (IL-1Ra), anakinra, a clinically approved agent. A diet with high amounts of phytoestrogens, such as flaxseed (Flax), genistein (GEN), and the mammalian lignan enterolactone (ENL), may affect breast cancer progression in a similar fashion as the antiestrogen tamoxifen. Both cancer cells and tumor stroma may be targets for cancer therapy. By using microdialysis in a model of human breast cancers in nude mice, we could perform species-specific analyses of released proteins in the microenvironment. We show that tumors treated with tamoxifen and fed Flax or ENL exhibited decreased in vivo release of IL-1β derived from the murine stroma and decreased microvessel density whereas dietary GEN had no effects. Cancer cell-released IL-1Ra were approximately 5 times higher than stroma-derived IL-1Ra. Tamoxifen, Flax, and ENL increased IL-1Ra levels significantly whereas GEN did not. The tumor stroma contained macrophages, which expressed the estrogen receptor. In vitro, estradiol decreased IL-1Ra released from breast cancer cells and from cultured macrophages. IL-1Ra decreased endothelial cell proliferation significantly in vitro whereas breast cancer cell proliferation was unaffected in presence of estradiol. Finally, IL-1Ra therapy of tumor-bearing mice opposed estrogen-dependent breast cancer growth and decreased angiogenesis. We conclude that the release of IL-1s both by cancer cells and the stroma, where macrophages are a key component, may offer feasible targets for antiestrogen therapy and dietary interventions against breast cancer.
- Journal
- Cancer Res
- Publish Year
- 2011
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Tamoxifen, flaxseed, and the lignan enterolactone increase stroma- and cancer cell-derived IL-1Ra and decrease tumor angiogenesis in estrogen-dependent breast cancer
- Bilingual Status
- semi_complete