In vitro modeling of tumor spheroid interactions to perfused blood vessels

Tumor angiogenesis, the formation of new blood vessels from existing blood vessels in and around the tumor stroma, is orchestrated by multiple biological factors in the tumor microenvironment, including tumor stromal cells, extracellular matrices, and secreted growth factors. Here, we present the processes to define and optimize the biological conditions for robust interactions between tumor spheroids and engineered blood vessels in a microfluidic organ-on-a-chip device in vitro. Within the device, vascular lumen formation and vessel sprouting in human umbilical vein endothelial cell based engineered blood vessels are observed in a variety of extracellular matrices (collagen, Matrigel, and fibrin), containing metastatic breast tumor cells (MDA-MB-231), and tumor stromal cells (mesenchymal stem cells, and human lung fibroblasts) to show the crosstalk between the tumor spheroids and the perfused blood vasculatures in vitro.

Boosting the abscopal effect of radiotherapy: a smart antigen-capturing radiosensitizer to eradicate metastatic breast tumors

A smart antigen-capturing radiosensitizer based on hollow mesoporous titanium dioxide (HTiO2) has been developed for metastatic breast tumor treatment.

Biochemical and Anti-Triple Negative Metastatic Breast Tumor Cell Properties of Psammaplins

Breast tumors reprogram their cellular metabolism, nutrient uptake, and utilization-associated biochemical processes. These processes become further transformed as genetically predisposed metastatic breast tumor cells colonize specific organs. Breast tumor cells often metastasize to the brain, bone, lung and liver. Massagué and colleagues isolated organotropic subclones and established organ-specific gene signatures associated with lung-, bone-, and brain-specific metastatic triple-negative breast cancer (TNBC) MDA-MB-231 cells. Using these genetically characterized metastatic subclones specific to lung (LM4175), bone (BoM1833), and brain (BrM-2a), we evaluated marine natural products for the ability to differentially suppress metastatic breast cancer cells in a target organ-dependent manner. Psammaplin-based histone deacetylase (HDAC) inhibitors were found to differentially inhibit HDAC activity, induce activation of hypoxia-inducible factor-1 (HIF-1), and disrupt organotropic metastatic TNBC subclone growth. Further, psammaplins distinctly suppressed the outgrowth of BoM1833 tumor spheroids in 3D-culture systems. Similar results were observed with the prototypical HDAC inhibitor trichostatin A (TSA). These organotropic tumor cell-based studies suggest the potential application of HDAC inhibitors that may yield new directions for anti-metastatic breast tumor research and drug discovery.