Lipocalins and cancer.

Lipocalins are mainly extracellular carriers of lipophilic molecules, though exceptions with properties like prostaglandin synthesis and protease inhibition are observed for specific lipocalins. The interest concerning lipocalins in cancer has so far been focussed to the variations in concentration and the modification of lipocalin expression in distinct cancer forms. In addition, lipocalins have been assigned a role in cell regulation. The influence of the extracellular lipocalins on intracellular cell regulation events is not fully understood, but several of the lipocalin ligands are also well-known agents in cell differentiation and proliferation. Lipophilic ligands can, after lipocalin-mediated transport to the cell surface, penetrate the cell membrane and interact with proteins in the cytosol and/or the nucleus. The signaling routes of the lipocalin ligands, retinoids and fatty acids are presented and discussed. Tumor growth in tissue is restricted by extracellular protease/protease inhibitor interactions. Several lipocalins also have protease inhibitory properties and possess the ability to interact with tumor specific proteases, revealing another pathway for lipocalins to interact with cancer cells.