Colon-cancer liver metastasis is effectively targeted by recombinant methioninase (rMETase) in an orthotopic mouse model

Kentaro Miyake; Qinghong Han; Takashi Murakami; Tasuku Kiyuna; Kei Kawaguchi; Kentaro Igarashi; Thinzar M Lwin; Masuyo Miyake; Jun Yamamoto; Michael Bouvet; Itaru Endo; Robert M Hoffman

doi:10.1016/j.tice.2023.102125

Colon-cancer liver metastasis is effectively targeted by recombinant methioninase (rMETase) in an orthotopic mouse model

Tissue Cell. 2023 Aug:83:102125. doi: 10.1016/j.tice.2023.102125. Epub 2023 Jun 2.

Authors

Affiliations

¹ AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: kmkmkm@med.yokohama-cu.ac.jp.
² AntiCancer, Inc., San Diego, CA, USA.
³ AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁴ AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA.
⁵ Department of Surgery, University of California, San Diego, CA, USA.
⁶ Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: endoit@med.yokohama-cu.ac.jp.
⁷ AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.

PMID: 37320867
DOI: 10.1016/j.tice.2023.102125

Abstract

Background: Colorectal cancer liver metastasis (CCLM) is the most frequent cause of death of colorectal cancer. Development of novel new effective therapy is needed for CCLM patients to improve outcome. The aim of the present study was to investigate the efficacy of recombinant methioninase (rMETase) on a CCLM orthotopic mouse model of liver metastasis established using the human colon cancer cell line HT29 expressing red fluorescent protein (RFP).

Materials and methods: Orthotopic CCLM nude mouse models were randomized into two groups: control group (n = 6, PBS 200 µl, i.p., daily); rMETase group (n = 6, 100 units/200 µl, i.p., daily). Tumor volume was measured on day 0 and day 15. Body weight was measured twice a week. All mice were sacrificed on day 15.

Results: rMETase significantly inhibited the increase of the liver metastasis as determined by RFP fluorescence area and intensity (p = 0.016 and 0.015, respectively). There was no significant difference of body weight between either group on any day.

Conclusions: The present study suggests that rMETase has future potential therapy for CCLM in the clinic.

Keywords: Colon cancer; Hoffman effect; Liver metastasis; Methionine addiction; Orthotopic mouse model; Recombinant methioninase.

MeSH terms

Animals
Body Weight
Colonic Neoplasms* / drug therapy
Colonic Neoplasms* / pathology
Humans
Liver Neoplasms* / drug therapy
Mice

Substances

L-methionine gamma-lyase