MMPs are mostly produced by TAMs, released into the extracellular space as inactive zymogen, and subsequently cleaved and activated by other proteinases.29 MMP-9, for example, directly releases glycocalyx-bound VEGF from cell membranes and decreases the amount of syndecan-4 which binds and inactivates VEGF.58 The substantially reduced MMP activity in Gpr35–/– tumours corroborates a role of this GPCR as an upstream regulator of tumour tissue remodelling. The gene discussed is SDC4; the disease is neoplasm.