This surprising result arose from the observation that expression of β-defensin 29 (DEFB29) by ID8 mouse ovarian cancer cells markedly accelerated tumour growth when these cells were transplanted subcutaneously in mice, but only when the cells also co-expressed high levels of vascular endothelial growth factor (VEGF; also known as VEGF-A). ID8 VEGF+DEFB29+ tumours contained more blood vessels than ID8 VEGF+ tumours, indicating that DEFB29 functions with VEGF to promote tumour angiogenesis.
Because β-defensins are known to be chemoattractive for DCs, the authors analysed expression of the DC marker CD11c in ID8 VEGF+DEFB29+ tumours. CD11c+ cells were found in capillary-like structures and were shown to have an immature DC phenotype, but they were also found to express endothelial-cell markers, such as CD34 and VE-cadherin. These CD11c+ cells were shown to be responsible for the increased tumour growth by comparing ID8 VEGF+ cells transplanted alone or mixed with CD11c+ cells from ID8 VEGF+DEFB29+ tumours. Further experiments showed that tumour-derived CD11c+ cells can form blood-vessel-like structures in vitro and in vivo, without proliferation (ruling out the involvement of a stem-cell population), confirming that the CD11c+ cells increase tumour growth through vasculogenesis. Interestingly, tumour-infiltrating CD11c+ cells could present antigen to T cells when removed from the tumour milieu in vitro, showing that these cells can function as endothelial-like cells or DCs depending on the environment.
This is a preview of subscription content, access via your institution
