In the B2B device, just as in real life, the metastatic process starts within a primary tumor. Indeed, the device hosts a patient-derived breast cancer lesion in a dedicated chamber, which is developed by the Cancer Metastasis group led by Nicola Aceto at the University of Basel.
“We designed the breast cancer chamber so that it is as close to reality as possible”, explains Prof. Aceto. “First, it hosts a 3D growing tumor mass, as opposed to more static systems which usually enable the proliferation only in two dimensions.” In B2B instead, the tumor mass can grow autonomously in three dimensions, mimicking the spontaneous behavior of a tumor. “To increase the resemblance,” continues Nicola, “we opted for patient-derived circulating tumor cells. The classic cancerogenic cell lines have been propagated for so many years that they have adapted over time. Our patient-derived cells are instead grown in the lab for the minimum amount of time and then placed directly into the device, where they continue to grow.”
The B2B breast cancer lesion has also a network of self-assembled capillaries that connect the tissue to a network of larger artificial vessels (more here). To develop these natural capillaries, “we will include within the tumor mass some endothelial cells –cells that naturally form blood vessels – and as the tumor grows, they will grow too and form a microcapillary network.” This network is then put in contact with the macro network, developed by the University of Maastricht. The smooth transition from small natural vessels to big artificial ones is one of the most critical and innovative features of the B2B device (more here).
Finally, thanks to the B2B concept the extravasation of cells is spontaneous and not forced by the system. “We expect that some cancer cells will recognize the presence of blood vessels and they will spontaneously migrate there and join the systemic circulation” says Nicola “While we are fairly positive that this phenomenon will happen, its frequency might depend on several factors e.g. how invasive the primary cells are, how many capillaries there are in the system, what is the micro-environment, etc.” These parameters might be used later on to fine-tune the system and modulate the metastasis frequency.