Fish oil prevents breast cancer cell metastasis to bone

The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω−3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.

Research highlights
► Fish oil diet arrests bone metastasis of breast cancer cells in mice.
► Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), effectively block migration and invasion of the highly metastatic human breast cancer cells, MDA-MB-231.
► The prometastatic cell adhesion protein CD44 is the target of DHA and EPA in breast cancer cells.
► Fish oil diet successfully decreased extremely potent metastasis-inducing protein CD44 mRNA and protein expression in the tumor tissue.