Lysophosphatidylcholine attenuates melanoma cell adhesion and migration dependent on the degree of fatty acid saturation.

Metastatic dissemination of tumor cells is the most destructive complication in cancer diseases. During metastasis, tumor cells invade the blood, interact with blood components like platelets and leukocytes, arrest at the endothelial surface of distant organs, and finally transmigrate through the endothelium to proliferate in the tissue matrix. Since adhesion receptors are crucially involved in all these steps, the blockade of adhesion receptors appears to be a promising strategy to interfere in this fatal cascade. Recently, we have observed antimetastatic effects of empty liposomes consisting of saturated phospholipids (PLs) in orthotopic pancreatic cancer nude mouse models [1]. Further studies confirmed saturated lysophosphatidylcholine (sLysoPC) as the active agent, which probably arises in high local concentrations in the tumor tissues as a degradation product from the saturated PLs of the liposomes based on their passive tumor accumulation due to their enhanced permeability and retention effect (EPR) [2, 3]. sLysoPC concentration of 450 μmol/L, which is only slightly higher than normal plasma levels (~ 300 μmol/L), induced morphological changes, reduced cell adhesion of murine B16.F10 melanoma cells in vitro, and led to a pronounced reduction of their metastatic lung invasion in vivo [4, 5]. The reduced capacity of sLysoPC-treated B16.F10 cells for receptor-mediated cell contact formation (e.g., P-selectin-mediated platelet binding, and endothelial contacts the integrin via VLA-4), appears to be pivotal for the diminished metastatic like lung invasion [5]. Nonetheless, the molecular mode of action of sLysoPC leading to reduced adhesion receptor activity and alleviated metastatic burden in mice remains elusive. However, a deregulation of tumor membrane properties, most likely due to a rigidification, appears probable. To follow this hypothesis and obtain first insights, the present study compares a saturated and an unsaturated LysoPC derivative in their impact on receptor-mediated adhesion and migration of human MV3 melanoma cells.