What brings pericytes to tumor vessels?

Abstract

Paracrine signaling via platelet-derived growth factor B (PDGFB), expressed by endothelial cells, and its receptor PDGFR-beta, expressed by pericytes, plays a central role in blood vessel maturation. A new study (see the related article beginning on page 1142) reveals that it is not just the presence of PDGFB, but how it is presented to pericytes, that determines the quality of the endothelium-pericyte interaction.

Figure 1

MC recruitment to tumor vessels depends on a putative gradient of PDGFB. (a) PDGFB, secreted by an EC tube, has higher concentration near the tube, as shown in the small graphs. (b) Normally, MCs, which express PDGFR-β, sense the PDGFB concentration gradient and move in to closely contact the ECs. (The basement membrane is not shown.) (c) If MCs do not express PDGFR-β, then they are not recruited. (d) Modifying PDGFB to remove its matrix retention eliminates the PDGFB concentration gradient and results in poor EC-MC contact. (e) If tumor cells express PDGFB, the PDGFB concentration in the tumor overwhelms the peri-EC gradient and EC-MC contact remains poor. (f) Perivascular cells expressing GFP under the control of the VEGF promoter surround vessels in the tumor interior. The image was obtained using a two-photon microscope. Orange, vessel lumens; green, MCs. Panel f is reproduced with permission from Nature Medicine (8).