Abstract
Introduction: Inflammation is associated with the accumulation of lactate at sites of tumour growth and inflammation. Lactate initiates tissue responses contributing to disease. We discuss the potential of targeting lactate transporters in the treatment of cancer and inflammatory conditions.
Areas covered: Lactate is the product of glycolysis, which is considered to be a waste metabolite and a fuel for oxidative cells. It is also an active signalling molecule with immunomodulatory and angiogenic properties. They are the consequence of lactate binding to membrane receptor(s) or being transported through specific carrier-mediated transporters across the cellular membrane. Carriers are distinct in proton-linked monocarboxylate transporters (MCTs) and Na+-coupled electrogenic transporters (SMTCs), expressed by several tissues including immune system, endothelium and epithelium. Several tumours and inflammatory sites (i.e., arthritic synovium, atherosclerotic plaque) show accumulation of lactate and altered expression of its transporters, thus suggesting a role of this metabolite in cancer and inflammatory disorders. We review the most recent evidence on lactate biology, focusing on transporter expression and function in health and disease.
Expert opinion: Lactate-initiated signalling is gaining attention for its implications in cancer and inflammation. This review deals with the therapeutic potential of targeting lactate transporters and drugs that are already in clinical use for cancer and discusses the opportunity to develop new therapeutics for inflammatory disease based on recent findings.
Original language | English |
---|---|
Journal | Expert Opinion on Therapeutic Targets |
Early online date | 14 Aug 2018 |
DOIs | |
Publication status | Published - Aug 2018 |
Keywords
- lactate
- lactate transporter
- inflammation
- metabolism
- immunity
- cancer