A new study has reported that morphine promotes breast cancer cell migration despite the lack of morphine receptors in such cells. Pain medication given after surgery in general and opioids in particular have been reported to influence risk of metastasis after primary cancer surgery. The NET1 gene has been shown to promote migration in cancer cells, which is one of the early steps in metastasis.
In the study, the authors investigated opioid receptor expression in breast cancer cell lines, as well as the direct effect of morphine and NET-1 on breast cancer cell migration. Hormone receptor negative (ER-/PR-) MDA-MB-231 and hormone receptor positive (ER+/PR+) MCF7 breast cancer cells were incubated with various concentrations of morphine and assessed for proliferation and migration. NET1 gene expression was determined and the effect of NET1 on cell migration was studied. In addition, the effect of morphine on NET1 expression and migration of cells with silenced NET1 was investigated.
The NET1 gene was found to be expressed in both breast cancer cell lines. NET1 expression was reduced by 96% after gene silencing in both cell lines, with corresponding reductions in cell migration. Despite a lack of opioid receptor expression in the cells, incubation with morphine was found to increase the expression of NET1 (by 94% in MCF7 and by 263% in MDA-MB-231 cells). Morphine increased migration by 17 to 27% in MCF7 and 7 to 53% in MDA-MB-231 cells. Silencing the NET1 gene was shown to extinguish the effect of morphine on migration. The authors conclude that the NET1 gene, but not opioid receptors, is expressed in breast cancer cells and may facilitate their migration. Morphine increases both expression of NET1 and cell migration, but not when the NET1 gene is silenced. The results imply that NET1 has a role in mediating the stimulative effect of morphine on breast cancer cell migration.