Nina Anseeuw

In the tumor tissue, cancer-associated fibroblasts (CAFs) accumulate closer to cancer cells, and change the mechanical properties of the tumor microenvironment (TME) through their interaction with the extracellular matrix (ECM) [1]. They adhere to the ECM through integrin receptors and use cellular contractility to apply force onto these adhesions, causing cell-mediated deformation of the matrix, which contributes to the stiffening of tumor stroma. As a response, the surrounding tumor cells sense the above-mentioned mechanical changes and transduce these mechanical cues into intracellular biochemical signals [2]. Therefore, CAFs play a key role in tumor growth and pave the way for cancer cells to initiate metastasis and invasion of other tissues[3]. While the effect of CAFs on the TME is well studied, less is known concerning the propagation of mechanical signals through the matrix, from the CAFs to cancer cells, and their effects on cell behavior. In this project, we will employ the unique, fully biomimetic polyisocyanide (PIC) hydrogel, with fibrous structure and strain-stiffening behavior, to establish a co-culture model for fibroblasts and colon cancer cell spheroids[4]. The influence of fibroblast activation on cancer cell behavior will be systematically investigated. The result will have a high impact on understanding how cancer process and enhance the current treatment methods by providing more diverse targets for cancer therapies. Last but not least, the student will work in a multicultural and multidisciplinary environment, and gain expertise in 3D cell culture, mechanobiology, advanced fluorescence microscopy and biomaterials (functionalization and characterization).