Another hypothesis to explain this ‘paradox’ is that elevated serum endostatin mostly reflects ongoing angiogenesis, as it is known that (i) matrix metalloprotease, which is activated during angiogenesis, can cleave collagen and modify its structure (Xu et al, 2001; Hangai et al, 2002), and (ii) collagen XVIII is mainly synthesised in the perivascular basement membrane of tumour-associated blood vessels (Muragaki et al, 1995; St Croix et al, 2000; Guenther et al, 2001). The gene discussed is COL18A1; the disease is neoplasm.