Mechanisms of Tumor-Lymphatic Interactions in Invasive Breast and Prostate Carcinoma

• Published in: International journal of molecular sciences 2020-01, Vol.21 (2), p.602
• Main Authors: Oliveira-Ferrer, Leticia, Milde-Langosch, Karin, Eylmann, Kathrin, Rossberg, Maila, Müller, Volkmar, Schmalfeldt, Barbara, Witzel, Isabell, Wellbrock, Jasmin, Fiedler, Walter
• Format: Article
• Language: English
• Subjects: Angiogenesis; Breast cancer; Cell adhesion; Cell adhesion & migration; Cell culture; Cell cycle; Chemokines; co-culture; Complement component C1r; Complement component C3; Complement system; Cytokines; E-selectin; Endothelial cells; Endothelium; Gene expression; Genes; Glycosylation; Hyaluronic acid; Invasiveness; Ligands; lymphatic endothelial cells; lymphatic metastasis; Lymphatic system; Metastases; Metastasis; Molecular modelling; Motility; mRNA; Prostate cancer; Prostate carcinoma; Tumor cell lines; Tumor cells; Tumors; Vascular endothelial growth factor
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21020602

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.