Microfluidic studies for monitoring the metastatic cascade and cancer-immune cells interaction

Metastases are the primary cause of death in cancer patients. Small animal models are helping dissecting some key features of the metastatic cascade but many bio-mechanic details remains difficult to analyze in vivo. For this reason a series of tools for performing systematic analysis of vascular permeability, tissue architecture, blood flow, biochemical stimuli and inflammation were produced in the last decade. Particularly relevant for this field is the use of microfluidic chips allowing to include in vitro models a vascular component. During my PhD, I applied this novel technologies to replicate in vitro key steps in the metastatic cascade and cancer-immune cell interaction with a focus on the establishment of microfluidics for metastasis. More specifically I used 3 different microfluidic chips: i) a single-channel microfluidic chip allowing to study CTCs adhesion and rolling inside a small capillary; ii) a double-channel microfluidic chip, composed by an upper and a lower channels mimicking the vascular and extravascular compartments; the channels are laterally connected by an array of micro pillars acting as a vascular membrane; iii) a three channel device composed by a central 3D culture of tumor cells embedded into a collagen matrix flanked by 2 channels connected to the former by a series of trapezoidal pillars. The two lateral compartments are used to simulate the vascular and stromal environment respectively. In the text we show how the aforementioned microfluidic devices can efficiently recapitulate in vitro multiple key steps of cancer metastatic cascade and some of the most important interactions between immune-cancer cell interactions.