During the last few years, diverse studies have shown that
tumors can actively interact with the lymphatic system and promote
metastases development. In order to examine the molecular mechanisms involved in this interaction, we co-cultured
tumor and lymphatic endothelial cells (LEC) and subsequently analyzed the molecular alterations of LECs. Therefore, LECs were co-cultivated with either a highly or weakly metastatic
breast cancer cell line using contact (mixture) and non-contact (transwell) co-cultures.
mRNA profiles from LECs were subsequently analyzed for genes specifically induced by highly metastatic
tumor cells ("metastatic specific"). Among the up-regulated "metastatic specific" genes, we found candidates involved in cell cycle, cell adhesion and motility (BST2,
E-selectin, and HMMR),
cytokines (CCL7, CXCL6, CXCL1, and CSF2) and factors of the
complement system (C1R, C3, and CFB). Among the down-regulated genes, we detected the
hyaluronan receptor STAB2,
angiogenic factor apelin receptor (
APLNR), and the glycosylation
enzyme MAN1A1. In an additional
prostate cancer co-culture model, we could confirm a "metastatic specific" upregulation of
E-selectin and CCL7 in LECs after interaction with the
prostate cancer cell lines LNCAP (highly metastatic) and DU145 (weakly metastatic). These data allowed us to identify a set of genes regulated in LECs during in vitro communication with
cancer cells, which might subsequently facilitate
lymphatic metastasis.