18:40 - 19:15
Room: Oregon Ballroom
Rapid Fire Abstract Session (Non-CME)
Chair/s:
Barbara Pockaj, Isaac P. Witz
TGF-b1-induced EMT promotes dendritic cell properties and lymphatic dissemination of cancer cells
Jonas Fuxe, Mei-Fong Pang, Nikolina Giotopoulou, Mikael Karlsson, Anna-Maria Georgoudaki

Background: The lymphatic system is a major gateway for tumor cell dissemination in breast cancer and many other forms of cancer. Yet, it is not clear how tumor cells find their way into lymphatic vessels and whether this is a regulated process, or more of a stochastic event. Recently, we found that mammary tumor cells undergoing TGF-b1-induced epithelial-mesenchymal transition (EMT) become activated for targeted migration through the lymphatic system via CCR7/CCL21-mediated chemotaxis. Furthermore, we found that tumor cells undergoing TGF-b1-induced EMT acquire properties of immune cells. Based on these results we hypothesize that EMT is an activation step, which activates tumor cells for chemotactic migration towards inflammatory signals, similar to how dendritic cells (DCs) become activated for targeted migration through the lymphatic system during inflammation.

Materials and Methods: To expand on this concept we have performed gene-profiling analysis to analyze immune cell features of tumor EMT cells. We have also developed a 3D-based co-culture assay to study the capacity of EMT cells to migrate towards lymphatic versus vascular endothelial cells. In addition, we have used a footpad model in the mouse to determine how DC properties of EMT cells affect their capacity to home to draining lymph nodes.

Results: Gene profiling experiments indicate that tumor cells undergoing EMT express a DC signature. Several genes within this signature have previously been associated with DC migration, but not with EMT or lymphatic spread of cancer cells. Knockdown of these genes affect the capacity of tumor EMT cells to migrate towards lymphatic endothelial cells in 3D cultures, and to disseminate through the lymphatic system, in vivo.

Conclusions: We propose that breast cancer cells undergoing TGF-b-induced EMT acquire properties of DCs allowing them to migrate in a targeted fashion through the lymphatic system.


Reference:
21-01
Session:
Session 21: Rapid Fire Abstract Session: Tumor Microenvironment and Cancer Progression
Presenter/s:
Jonas Fuxe
Presentation type:
Rapid Fire Oral Presentation
Room:
Oregon Ballroom
Chair/s:
Barbara Pockaj, Isaac P. Witz
Date:
Friday, April 21, 2017
Time:
18:40 - 18:45
Session times:
18:40 - 19:15