Single-cell transcriptome analysis reveals reciprocal epithelial and endothelial cell evolution in ovarian cancer

Summary: 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.