HPGD and colorectal carcinoma: One explanation for high PGE2 levels in the presence of increased 15-PGDH protein expression in CRCLM, combined with the contrasting in vitro findings, is that 15-PGDH activity could be compromised by limiting amounts of NAD+ in a chronic hypoxic tumour microenvironment, with acute induction of 15-PGDH in HCA-7 human CRC cells being associated with a reduction in overall PGE2 production, possibly because there are sufficient cellular NAD+ stores to maintain efficient PGE2 catabolism in the acute setting.