Response of Triple-negative Breast Cancer Liver Metastasis to Oral Recombinant Methioninase in a Patient-derived Orthotopic Xenograft (PDOX) Model

Hye In Lim, Jun Yamamoto, Qinhong Han, Yu Sun, Hiroto Nishino, Yoshihiko Tashiro, Norihiko Sugisawa, Yuying Tan, Hee Jun Choi, Seok Jin Nam, Michael Bouvet, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background/Aim: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. Materials and Methods: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. Results: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). Conclusion: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse body-condition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease.

Original languageEnglish
Pages (from-to)3163-3169
Number of pages7
JournalIn Vivo
Volume34
Issue number6
DOIs
Publication statusPublished - 2020 Nov
Externally publishedYes

Keywords

  • Ascites
  • Liver metastasis
  • Lymph node
  • Oral recombinant methioninase
  • PDOX
  • Patient-derived orthotopic xenograft
  • Re-metastasis
  • TNBC
  • Treatment
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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