Methionine enkephalin suppresses lung cancer metastasis by regulating the polarization of tumor-associated macrophages and the distribution of myeloid-derived suppressor cells in the tumor microenvironment and inhibiting epithelial-mesenchymal transition.

Metastasis is one of the most difficult challenges for clinical lung cancer treatment. Epithelial-mesenchymal transition (EMT) is the crucial step of tumor metastasis. Immune cells in the tumor microenvironment (TME), such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), promote cancer cell EMT. In this study, we explored the effect of methionine enkephalin (MENK) on the EMT process in vitro and in vivo, and its influence on TAMs, MDSCs, and associated cytokines in vivo. The results showed that MENK suppressed growth, migration, and invasion of lung cancer cells and inhibited the EMT process by interacting with opioid growth factor receptor. MENK reduced the number of M2 macrophages and MDSC infiltration, and downregulated the expression of interleukin-10 and transforming growth factor-β1 in both primary and metastatic tumors of nude mice. The present findings suggest that MENK is a potential target for suppressing metastasis in lung cancer treatment.