Mechanisms of tumor-lymphatic interactions in invasive breast and prostate carcinoma

Leticia Oliveira-Ferrer, Karin Milde-Langosch, Kathrin Eylmann, Maila Rossberg, Volkmar Müller, Barbara Schmalfeldt, Isabell Witzel, Jasmin Wellbrock, Walter Fiedler

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish
Article number602
JournalInternational Journal of Molecular Sciences
Volume21
Issue number2
DOIs
StatePublished - 2 Jan 2020
Externally publishedYes

Keywords

  • Breast cancer
  • Co-culture
  • Lymphatic endothelial cells
  • Lymphatic metastasis
  • Prostate cancer

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