Abstract 290: The role of tumor stromal topography-regulated genes in modulating the cellular landscape of tumor stroma in breast cancer

Abstract

Abstract The tumor remodels the surrounding extracellular matrix fibers to become topographically aligned at the tumor front, further facilitating cancer cell migration. Our recent studies show that aligned tumor stromal topography promotes the detachment of breast cancer cells from the main tumor, then, in the following cell migration, upregulating genes such as genes encoding the cytochrome P450 family 1 subfamily A member 1 (CYP1) and inhibitor of DNA binding (ID) proteins. In this study, we further explored the role of topography-regulated genes in modulating the cellular landscape of tumor stroma. By analyzing the correlation of topography-regulated genes with stromal cell infiltration in bioinformatics databases, we found significant positive correlations between the RNA expression levels of most topography-regulated genes and the infiltration levels of cancer-associated fibroblasts and endothelial cells. Notably, the strongest correlation was between the expression level of ID3 and the infiltration levels of cancer-associated fibroblasts (r = 0.509) and endothelial cells (r = 0.506). Additionally, ID3 remained highly expressed in circulating tumor cells but exhibited low expression at distant metastatic sites. These findings suggest that genes regulated by tumor stromal topography, especially ID3, may play a role in neovascularization and fibrosis of the tumor microenvironment and the survival adaptation of cancer cells in circulation, thereby promoting metastasis. Citation Format: Chia-Yi Su. The role of tumor stromal topography-regulated genes in modulating the cellular landscape of tumor stroma in breast cancer [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 290.