Abstract 5424: Respiratory function linked to in vivo metastatic lung cancer progression

Abstract

Abstract Metastases are a major cause of morbidity and mortality in patients with cancer. How metastatic tumors employ metabolic programs to successfully colonize diverse microenvironment is poorly understood. Using an orthotopic xenograft mouse model of lung cancer that develops metastases and recapitulates metastatic lung cancer spread, we injected GFP-LUC-expressing human H1975 lung tumor cells into the left lungs of mice. In vivo bioluminescence imaging was used to visualize tumor growth and metastatic spread for 30 days. Animals were then euthanized and primary and metastatic tumors were collected from different anatomical sites of the body (left lung, right lung, mediastinum, abdominal metastases). Tumor samples were analysed by RNA sequencing analysis. The transcriptomes of lung metastases demonstrated a significant reduction in the expression of genes encoding respiratory pathway protein as compared to the primary lung tumors, suggesting metabolic reprogramming of their respiratory metabolism. CRISPRi-mediated silencing of genes encoding components of respiratory function in human lung cancer cells was associated with significantly increased metastatic spread in vivo. These studies suggest the functional importance of respiratory metabolism on modulating in vivo disease spread. Citation Format: Padmini Bisoyi, Yoshi Sei, Neal Bennett, Ken Nakamura, Jean L. Nakamura. Respiratory function linked to in vivo metastatic lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5424.