“Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop”
“Breast Cancer Cells and Macrophages in a
Thursday, November 8, 2018
MBG Conference Hall
Prof. Dr. Devrim Pesen Okvur
Izmir Institute of Technology, Deparment of Molecular Biology and Genetics
Devrim Pesen Okvur received her Ph.D. degree in Cellular and Molecular Physiology from the Johns Hopkins University in 2005. After postdoctoral studies at the Karolinska Institute, Royal Institute of Technology and Albert Einstein College of Medicine, she joined the faculty of Izmir Institute of Technology in 2010. Her research focuses on design and fabrication of lab-on-a-chips that mimic the cellular microenvironment and biophysical and micro-environmental control of cell adhesion, migration and invasion in breast cancer. Her research has been funded by a FP7 Marie Curie Grant and several TUBITAK grants. She is also one of the recipients of TÜBA-GEBİP 2016 and BAGEP 2016 awards. She has published papers on cell biophysics, nanobiotechnology, microfabrication and has patents granted/pending on lab-on-a-chip devices for cell biology. She is also the co-founder of İNİTİO Biomedical Engineering Consulting Tra. Ind. Co. Ltd. specializing in lab-on-a-chip devices for cancer cell biology.
Cancer cells and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by cancer cells. Despite contradictory findings, this interaction is perceived as a paracrine loop. Yet, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of MDA-MB-231 breast cancer cells (BCC) with RAW264.7 macrophages in 2D and 3D. BCC did not show chemotaxis to macrophages in custom designed 3D cell-on-a-chip devices, which was in agreement with ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in matrigel and collagen showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages reduced and promoted migration of BCC in matrigel and collagen, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC-derived-CSF-1 whereas BCC required direct contact to interact with macrophage-derived-EGF. In conclusion, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively.