Resumen de Development of microfluidic systems applied to cancer research
Cancer is the main mortality cause in the developed world and the second in developing countries. However, while our knowledge about the cancer cell and molecular biology has increased, drug discovery rate has dramatically dropped in the last decades. Traditional cell culture models rely on the use of the Petri dish, where cells grow on a flat plastic surface. Although these models are robust and they have been extensively used, they lack of the complexity of the biological structures.
In this context, microfluidic models present an excellent alternative to bridge this gap between in vivo and in vitro research. Thereby, in this PhD thesis, different microfluidic models have been developed to study tumor cell behavior under scenarios that try to mimic more faithfully the physiologic conditions. Firstly, a brief introduction about cancer biology and microfluidics is described in chapter 1. In chapter 2, a preliminary model of tissue composed of a three dimensional extracellular matrix, provided of lateral microchannels to mimic the blood vessels, was developed as a proof of concept. Afterwards, in chapter 3, this model was used to study the invasion of the most common and lethal brain tumor, the Glioblastoma. Results demonstrated that nutrient starvation was able to trigger the invasion process and enhance the tumor cell´s aggressiveness. On the next chapter, the different mechanisms of tumor invasion were studied, showing the differences between collective invasion and isolated migration. In chapter 5, the effects of nutrient and oxygen gradients on tumor drug response were studied. Finally, the main conclusions of this PhD thesis are shown in chapter 6.
