2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.02G.01 Differentiation and Metabolic Phenotypes of Lung Squamous Cell Carcinoma Organoids are Modified by the Tumor Microenvironments

EP.02G.01 Differentiation and Metabolic Phenotypes of Lung Squamous Cell Carcinoma Organoids are Modified by the Tumor Microenvironments

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This study investigates how the tumor microenvironment affects the differentiation and metabolic phenotypes of lung squamous cell carcinoma organoids. By using patient-derived xenograft (PDX) models, researchers established lung cancer organoids under controlled culture conditions. Microenvironmental impacts were tested by comparing subcutaneous and orthotopic (lung) injection sites in non-obese severe combined immune deficient gamma (NSG) mice. <br /><br />Key findings revealed that the subcutaneously injected organoids grew significantly faster than those injected into the lung. Pathological differences were notable, with orthotopic lung tumors showing poorly differentiated, non-keratinizing phenotypes, whereas the subcutaneous tumors exhibited moderately differentiated keratinizing characteristics. Stronger expression of squamous cell markers, such as P63 and SOX2, was observed in subcutaneous tumors, supported by immunohistochemistry results.<br /><br />Gene expression analysis via RNA sequencing revealed 2,406 differentially expressed genes (DEGs) between subcutaneous and lung tumors. However, differences in gene expression were minimal (44 DEGs) when analyzing newly established organoids from these tumor types, indicating significant tumor plasticity. The study highlighted the upregulation of MTORC1 signaling, glycolysis, and hypoxia pathways in subcutaneous tumors.<br /><br />Overall, it concludes that lung squamous cell carcinoma differentiation and metabolic status are influenced by the tumor microenvironment, suggesting that cancer organoids serve as a vital model in understanding the molecular mechanisms and tumor plasticity regulated by environmental factors. This underscores the complexity of cancer biology and the potential of organoids in preclinical cancer research, paving the way for personalized medicine and targeted therapeutic interventions.

Asset Subtitle

Hiroyuki Ogawa

Meta Tag

Speaker Hiroyuki Ogawa

Topic Tumor Biology – Preclinical Biology

Keywords

tumor microenvironment

lung squamous cell carcinoma

organoids

patient-derived xenograft

NSG mice

differentiation

gene expression

MTORC1 signaling

tumor plasticity

personalized medicine