Reduced taurine synthesis underlies morphine-promoted lung metastasis of triple-negative breast cancer

Background The mechanisms underlying the progression and metastasis of triple-negative breast cancer (TNBC) in the context of extended morphine exposure remain poorly understood. Morphine consumption has been a pressing issue in many countries. While the physiological impact of extended morphine use is multifaceted, cancer patients with a history of prolonged morphine usage often result in poor prognosis. Methods In this study, we investigated the impact of extended morphine treatment on the transcriptional profiles of TNBC. To this end, mice were administered morphine intraperitoneally for 14 days followed by the implantation of EO771 cells, which are triple negative breast cancer cells, into their mammary fat pad. After primary tumors were removed on 38th day, a subset of mice were continuously giving saline or morphine until the 68th day. Tumor size, organ metastasis, and tumor RNA expression were analyzed. Results Our findings showed that prolonged exposure to morphine led to an increase in lung metastasis in the mouse model of triple-negative breast cancer. We conducted RNA sequencing analysis on tumors to compare their transcriptional profiles with or without metastasis. Through pathway analysis, we specifically examined the novel impact of morphine on the downregulation of taurine/hypotaurine biosynthesis. Given that morphine, droperidol (a dopamine receptor antagonist), and naloxone (an opioid receptor antagonist) might act through either opioid receptors or dopamine receptors, we further demonstrated that taurine mitigated EO771 cell invasion induced by morphine, but not by droperidol or naloxone treatment. Additionally, morphine treatment markedly decreased the expression of GAD1 , one of the enzymes essential for taurine biosynthesis, whereas droperidol and naloxone did not. Conclusion The findings of morphine-induced reduction in GAD1 level and the inhibition of invasion by taurine treatment suggest that taurine could serve as a potential supplement for triple-negative breast cancer patients who require morphine as part of their treatment regimen or due to their circumstances.