Tumours co-opt neighbouring blood vessels, along with vascular endothelial cells from those vessels, to support their own blood supply. They are also capable of attracting haematopoietic cells to build their own blood vessels. In the June issue of Nature Medicine, De Palma et al. have shown that it is possible to use these cells as a 'Trojan horse' to deliver suicide genes to the developing tumour.

Tumours produce growth factors that induce bone-marrow-derived endothelial progenitor cells to migrate to the tumour, where they contribute to the developing vasculature. To track these cells, DePalma et al. created lentiviral vectors that express green fluorescent protein (GFP) from promoter and enhancer sequences of the Tek gene, which encodes a receptor tyrosine kinase that is expressed almost exclusively in endothelial cells. The authors transduced a variety of cell types with the vector, and showed that GFP was expressed specifically in endothelial cells.

Mouse bone-marrow cells were transduced with the vector and transplanted back into their hosts. Within 12–24 weeks of transplantation, GFP was expressed by a small fraction of bone-marrow cells. Tumours were then grafted into these mice, and the GFP-expressing cells localized to the periphery of melanomas and other types of carcinomas. Here, they were closely associated with non-labelled endothelial cells into cord-like, laminar structures. There were fewer GFP-positive cells found in the inner tumour mass, but these were often associated with small blood vessels. De Palma et al. could not find evidence that the transduced cells developed into bona fide vascular endothelial cells. Rather, the cells expressed monocyte lineage markers and appeared to represent a subset of endothelial progenitors that promote angiogenesis by an unknown mechanism.

So, can these cells be used to deliver cell-death-inducing genes to tumours? DePalma et al. developed a 'suicide' vector containing a Tek promoter-driven thymidine kinase gene, which kills cells when expressed in the presence of gancyclovir. Bone-marrow cells were transduced with this suicide vector, transplanted back into mice and tested for their effects on tumour development. The vector-expressing cells again localized to the tumours, but on exposure to gancyclovir, were quickly cleared. At the end of the treatment phase, these tumours were much smaller and their vascular density was almost fivefold less than control tumours. There were no signs of myelotoxicity in treated mice.

DePalma et al. also checked to see if the transduced haematopoietic cells homed to other sites of neo-angiogenesis, such as to healing wounds. They found that after partial hepatectomy, Tie2/GFP-expressing cells localized to the granulation tissue that surrounds regenerating hepatic lobules. This cancer treatment might therefore disrupt wound-healing in patients.

The authors conclude, however, that haematopoietic cells are a useful vehicle for delivering gene-based therapies to tumours. The bone-marrow-derived cells that associate with the developing tumour vasculature will have to be better characterized, but other reagents designed to target these cells might be developed as antitumour agents.