Single-cell transcriptome analysis reveals reciprocal epithelial and endothelial cell evolution in ovarian cancer
Year: 2024
Type: article
Abstract: Tumor neovascularization mediated by endothelial cells (ECs) is essential for ovarian cancer (OC) progression, but interactions between epithelial cells and ECs are not well understood. Here, we analyze single-cell transcriptome of 87,847 epithelial cells and 11,696 ECs from fallopian tubes, primary and metastatic ovarian tumors. Cell differentiation trajectory analysis reveals that fallopian tube cells exhibit a potential development trend toward primary OC epithelial cells. We identify a sub-population of fallopian tube epithelial cells (FTSEC3), which highly express tumor cell markers and are enriched in vascular endothelial growth factor production. Two neovascularization-related EC phenotypes (MKI67+ proliferating ECs and ESM1+ tip cells) are specially found in ovarium tumors, which exhibit strong interactions with FTSEC3. We validate that genetic disruption of LAMININ and TGF-β with CRISPR in ECs inhibits sprouting angiogenesis. In summary, this study reveals a reciprocal evolution and interaction between epithelial and ECs in OC development and progression.
Source: iScience
Institutions: Chinese Academy of Sciences, University of Chinese Academy of Sciences, BGI Research, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang University of Technology, Aarhus University, Aarhus University Hospital, Steno Diabetes Center Aarhus, Wenzhou Medical University
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,150
OpenAlex ID: W4404516689