Adjuvant oral recombinant methioninase inhibits lung metastasis in a surgical Breast-cancer orthotopic syngeneic model

Background/Aim: In the present study, we evaluated the efficacy of adjuvant administration of oral recombinant methioninase (o-rMETase) against recurrence and metastasis in a 4T1 murine breast-cancer syngeneic model. Materials and Methods: 4T1 cells were orthotopically implanted into the 2nd mammary fat pad of BALB/c mice. The 4T1 orthotopic syngeneic models were randomized into 2 groups after primary tumor resection: untreated control and o-rMETase (100 units, oral, daily, 2 weeks). Results: The frequency and extent of local recurrence were reduced by o-rMETase. The number of individual cancer cells and metastatic nodules on the lung surface was significantly lower in the o-rMETase-treated mice than the untreated control mice. Conclusion: Adjuvant o-rMETase inhibited local recurrence and lung metastasis after primary tumor resection. Methionine addiction is possibly the most fundamental and general hallmark of cancer (1-9) and is tightly linked to other hallmarks of cancer (2). Methionine addiction was discovered in our laboratory and is due to increased rates of transmethylation compared to normal cells (3-6).