Speaker: Sophie Steinhäuser, PhD student. Department of Medical Anatomy, and Department of Laboratory Hematology, University of Iceland.
Title: Heterotypic interactions between endothelial cells and normal- and cancerous breast epithelial cells
Abstract: Investigating heterotypic interactions between cancer cells and the microvasculature is important for improving our understanding of how the microenvironment supports tumor growth and facilitates metastasis.Here, we analyze how isogenic non-tumorigenic vs. tumorigenic breast epithelial cell lines affect their vascular niche in 2D and 3D co-culture and how endothelial cells respond back to the epithelial cells. D492, D492M and D492HER2 are isogenic breast epithelial cells. D492 is a breast epithelial cell line with stem cell properties that in co-culture with endothelial cells undergoes epithelial to mesenchymal transition (EMT) that gave rise to D492M. Both D492 and D492M are non-tumorigenic D492HER2 was generated by overexpressing the HER2/ErbB2 oncogene in D492, is mesenchymal and shows tumorigenic properties.In both 2D and 3D co-culture with HUVEC endothelial cells, D492HER2 showed a greater physical interaction with HUVEC compared to D492. Migration assay confirmed increased migration of D492HER2 towards HUVECs. To assess crosstalk between epithelial cells and the HUVECs, conditioned media (CM) was collected from all three cell-lines. Treatment of HUVECs with CM from D492HER2 demonstrated increased 3D capillary network formation. Also CM from endothelial cells that had been pre-treated with CM from D492HER2 increased migration of D492HER2 cells.These data, although still descriptive, suggest that cancer cells do affect their endothelial niche and that cross-interaction with endothelial cells might be beneficial for cancer cells. Identification of candidate molecules mediating the cross-talk between endothelium and breast cancer cells could give valuable insights into a cancer-specific response of the vascular niche. To identify cancer cell-secreted factors and responsive endothelial target genes, secretome analysis and RNA sequencing of conditioned endothelial cells will be performed.