Endogenous arginase 2 as a potential biomarker for PEGylated arginase 1 treatment in xenograft models of squamous cell lung carcinoma

Oncogenesis
Sze-Kwan LamJames Chung-Man Ho

Abstract

Depletion of arginine induced by PEGylated arginase 1 (ARG1) (BCT-100) has shown anticancer effects in arginine auxotrophic cancers that lack argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). High levels of endogenous arginase 2 (ARG2) have been previously reported in human lung cancers. Although a high-ARG2 level neither causes immunosuppression nor affects disease progression, it may theoretically affect the efficacy of PEGylated ARG1 treatment. ARG2 was shown to be highly expressed in H520 squamous cell lung carcinoma (lung SCC) xenografts but undetectable in SK-MES-1 and SW900 lung SCC xenografts. We propose that high-endogenous expression of ARG2 could impede the anti-tumor effect of PEGylated ARG1 in lung SCC. The in vivo effect of PEGylated ARG1 was investigated using three xenograft models of lung SCC. PEGylated ARG1 (60 mg/kg) suppressed tumor growth in SK-MES-1 and SW900 but not H520 xenografts. ASS1 was expressed in SK-MES-1 and SW900 xenografts while OTC expression remained low in all xenografts. A high-endogenous ARG2 level was detected only in H520 xenografts. Serum arginine level was decreased significantly by PEGylated ARG1 in all xenografts. Nonetheless intratumoral arginine level was de...Continue Reading

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Citations

Jan 5, 2021·Chinese Medical Journal·Jin-Shou YangLei You
Jul 11, 2020·Cell·Michael A GilletteUNKNOWN Clinical Proteomic Tumor Analysis Consortium
Feb 2, 2021·Journal of Diabetes and Metabolic Disorders·Lakshmipathi VadlakondaAramati B M Reddy
Nov 16, 2021·Experimental Neurology·Abdelrahman Y FoudaRuth B Caldwell

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Methods Mentioned

BETA
xenografts
xenograft
ELISA
Assay

Software Mentioned

GelQuantNET
GraphPad
Prism

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