Pesen-Okvur, D. | Search bioRxiv

bioRxiv2020

Homing Choices of Breast Cancer Cells Revealed by Tissue Specific Invasion and Extravasation Lab-on-a-chip Platforms

Metastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of novel platforms to predict metastatic potential and homing choices of cancer cells. Here, two novel Lab-on-a-chip (LOC) platforms, invasion/chemotaxis (IC-chip) and extravasation (EX-chip), are presented for the quantitative assessment of invasion and extravasation, towards specific tissues. On IC-chip, invasive MDA-MB-231, but not non-invasive MCF-7 breast cancer cells invaded lung and liver microenvironments. Lung-specific but not bone-specific MDA-MB-231 clones efficiently invaded lung microenvironment, stressing ability of IC-chip to demonstrate different in vivo metastatic behaviors. On EX-chip, MDA-MB-231 cells extravasated more into the lung microenvironment compared to the liver and breast highlighting the potency of the platform to mimic in vivo homing choices. Overall, this study presents IC-chip and EX-chip that can determine tissue-specific invasion and extravasation potentials of cancer cells providing the groundwork for novel diagnostic tools to predict metastasis risk.

cancer biology↗

bioRxiv2020

Breast Cancer Cells and Macrophages in a Paracrine-Juxtacrine Loop

Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with 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 collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. We propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively.

cancer biology↗