Abstract 709: Metabolomic differences between pulmonary metastasis of Lewis lung carcinoma and normal lungs from C57BL/6 mice fed an obesogenic high-fat diet

Abstract

Abstract Metastasis, the spread of malignant cells from a primary tumor to distant organs, is the most devastating aspect of cancer. To understand the metabolism of metastases, we compared the metabolomes of pulmonary metastases of Lewis lung carcinoma (LLC) with that of normal lung tissues from mice fed an obesogenic high-fat diet. In a 2x2 design, male C57BL/6 mice, with or without a subcutaneous LLC inoculation, were fed the standard AIN93G diet or a high-fat diet (HFD), which provided 16% or 45% of energy from soybean oil, for 12 weeks. At the end of the study, lung metastases from injected mice and the lungs from non-injected mice were harvested for untargeted metabolomic analysis of primary metabolism by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). We identified 91 metabolites, 70 of which differed among the four groups. Pathway and network analyses along with the discriminant analysis showed that amino acid and carbohydrate metabolism were altered the most in metastases compared to the normal lung tissue (e.g., aminoacyl-tRNA biosynthesis pathways and the citric cycle). A 60% decrease in glutamine and a 25-fold elevation in sorbitol were observed in metastases. Cholesterol and its metabolite dihydrocholesterol were 50% lower in metastases than in the lungs. The HFD elevated arachidonic acid and its precursor linoleic acid in the lungs from non-LLC-bearing mice, which reflected dietary fatty acid composition of the HFD. However, such elevation did not occur in metastases from HFD-fed LLC-bearing mice, suggesting alterations in fatty acid metabolism during LLC metastatic progression. Differences in metabolomes between LLC pulmonary metastases and the normal healthy lungs identified in the present study can be useful in designing targeted studies for prevention and treatment of metastasis using this spontaneous metastasis model. Citation Format: Lin Yan, Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski. Metabolomic differences between pulmonary metastasis of Lewis lung carcinoma and normal lungs from C57BL/6 mice fed an obesogenic high-fat diet [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 709.