Data di Pubblicazione:
2021
Abstract:
Tumor vessel co-option is poorly understood, yet it is a resistance mechanism against anti-angiogenic therapy (AAT). The heterogeneity of co-opted endothelial cells (ECs) and pericytes, co-opting cancer and myeloid cells in tumors growing via vessel co-option, has not been investigated at the single-cell level. Here, we use a murine AAT-resistant lung tumor model, in which VEGF-targeting induces vessel co-option for continued growth. Single-cell RNA sequencing (scRNA-seq) of 31,964 cells reveals, unexpectedly, a largely similar transcriptome of co-opted tumor ECs (TECs) and pericytes as their healthy counterparts. Notably, we identify cell types that might contribute to vessel co-option, i.e., an invasive cancer-cell subtype, possibly assisted by a matrix-remodeling macrophage population, and another M1-like macrophage subtype, possibly involved in keeping or rendering vascular cells quiescent.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
anti-angiogenic therapy; cancer cells; endothelial cells; macrophages; metastasis; pericytes; resistance; single-cell RNA sequencing; tumor angiogenesis; tumor vessel co-option; Animals; Cell Line, Tumor; Endothelial Cells; Female; Kidney Neoplasms; Lung Neoplasms; Macrophages; Mice, Inbred BALB C; Myeloid Cells; Neoplasms; Pericytes; Single-Cell Analysis
Elenco autori:
Teuwen L.-A.; De Rooij L.P.M.H.; Cuypers A.; Rohlenova K.; Dumas S.J.; Garcia-Caballero M.; Meta E.; Amersfoort J.; Taverna F.; Becker L.M.; Veiga N.; Cantelmo A.R.; Geldhof V.; Conchinha N.V.; Kalucka J.; Treps L.; Conradi L.-C.; Khan S.; Karakach T.K.; Soenen S.; Vinckier S.; Schoonjans L.; Eelen G.; Van Laere S.; Dewerchin M.; Dirix L.; Mazzone M.; Luo Y.; Vermeulen P.; Carmeliet P.
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