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

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.