Single cell transcriptomics profiling of vessel co-option

Vessel co-option is an alternative mode of tumor vascularization, which contributes to resistance to anti-angiogenic therapy (AAT). In contrast to vessel sprouting (angiogenesis), knowledge about the mechanisms underlying vessel co-option is minimal, precluding therapeutic strategies. We therefore single-cell RNA-sequenced 31,964 cells from a murine lung metastasis model with vessel co-option, characterized by resistance to AAT. Unexpectedly, co-opted endothelial cells (ECs) were transcriptomically indistinguishable from healthy ECs and lacked an activation signature, while co-opted pericytes expressed a quiescence signature, in contrast to activated pericytes during angiogenesis. Compared with cancer cells during angiogenesis, co-opting cancer cells were phenotypically more diverse and enriched in invasive subpopulations. Together, these data reveal new insight into vessel co-option, with possible implications for the development of therapeutic targets.