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

Norihiko Sugisawa, Kazuyuki Hamada, H. A.N. Qinghong, Jun Yamamoto, S. U.N. Yu, Hiroto Nishino, Kei Kawaguchi, Michael Bouvet, Michiaki Unno, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

Abstract

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). Methionine overuse by cancer cells is called the “Hoffman effect”,

Original languageEnglish
Pages (from-to)4869-4874
Number of pages6
JournalAnticancer research
Volume40
Issue number9
DOIs
Publication statusPublished - 2020 Sep

Keywords

  • Adjuvant therapy
  • Breast cancer
  • Inhibition
  • Lung metastasis
  • Methionine restriction
  • Recombinant methioninase
  • Recurrence
  • Surgical resection

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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