Tumor-Stroma Interactions

Zhivka Hristova, Cindy Körner, Angelika Wörner, Sara Burmester, Birgitta Michels, Efstathios Vlachavas

The tumor microenvironment (TME) or tumor stroma comprises all cell types and extracellular matrix (ECM) that surrounds the tumor cells, jointly forming the tumor mass. The stromal compartment is comprised of immune cells from both, the innate and the adaptive systems, vascular cells, mesenchymal stem cells (MSC), cancer associated fibroblasts (CAF), and several other cell types. The TME affects tumor aggressiveness and the way tumor cells respond to therapies.

In several projects we are out to better understand how tumor and stromal cells impact on one another and cooperatively govern the phenotype of a particular cancer. Along these lines we have identified miR-1246 which is expressed in MSCs and regulates, via NF-KB signaling, the release of pro-inflammatory cytokines and chemokines (e.g., IL-6, CCL2, CCL5) [Bott et al. 2017]. We had previously identified miR-519a to confer resistance of luminal-like breast cancer to endocrine (tamoxifen) therapy [Ward et al. 2014]. More recently, we showed that the same miRNA also mediates apoptosis-resistance in breast cancer cells and their escape from recognition by natural killer (NK) cells [Breunig et al. 2017]. In collaboration with the group of Adit Ben-Baruch (Tel Aviv University) we showed that chemokine secretion is subtype-specific in breast cancer and that this is related to metastasis potential of tumors [Weitzenfeld et al., 2016, Liubimorski et al., 2019, Liubimorski et al., 2019, Dadiani et al., 2020].

Current research continues with MSCs and their interactions with tumor cells and extends towards the analysis of CAFs and immune cells in the context of breast cancer development and therapy response. To this end, we predominantly follow experimental in vitro and in vivo approaches [Berdiel et al., 2021, Maia et al., 2021].

Cytokine signaling: Adit Ben-Baruch (Tel Aviv)

Cell communication: Heidi Cerwenka (Mannheim)

Secretomics: Jeroen Krijgsveld (Heidelberg)

Clinics: Martina Vetter, Eva Kantelhardt (Halle/Saale), Andreas Schneeweiss (Heidelberg)