Microfluidic platform for cancer Intravasation: pass or no pass?

Projektbeschreibung

Mikrofluidische Plattform zur Untersuchung des intravasalen Eintrittsprozesses von Krebszellen

Krebs ist aufgrund von Metastasenbildung eine der häufigsten Todesursachen. Ein wichtiger Schritt in diesem Prozess ist die Intravasion, bei welcher Krebszellen in die Blutbahn eindringen und sekundäre Tumore bilden. Das vom Europäischen Forschungsrat geförderte Projekt Intrap soll erforschen, wie mechanische Faktoren diesen Prozess beeinflussen, da eine Verhinderung der Intravasation die Ausbreitung von Krebs verhindern könnte. Es soll untersuchen, wie mechanische Reize die Intravasation beeinflussen. Zu diesem Zweck wird es eine mikrofluidische Plattform mit Multi-Chip-Modellen von Blutgefäßen und extrazellulären Matrizen zur Untersuchung der Intravasation entwickeln. Mithilfe der Live-Mikroskopie sollen Erkenntnisse über die Metastasierung von Krebs gewonnen werden, die möglicherweise zur Entwicklung von Behandlungsstrategien beitragen können.

Ziel

Cancer still is one of the world’s deadliest diseases. Most devastating is the ability of cancer cells to spread throughout the body in a multistep process called metastasis, the major cause for mortality. A critical step is intravasation, when cancer cells pass a blood vessel wall to enter the blood stream, and travel to another location to create a secondary tumor. However, the mechanisms of intravasation are still largely unexplored, even though it is pivotal: if we can prevent it, cancer does not spread. Intrap aims to enhance our understanding of intravasation through a unique experimental approach.
We hypothesize that intravasation is critically controlled by mechanical cues like stiffness, geometry, and adhesive interactions; after all, the act of passing the vessel wall requires mechanical action of the cells: deforming, adhering, detaching, moving, and overcoming mechanical forces. We will take a systematic approach enabling to separately control different mechanical cues, and directly observe their effect on intravasation. The groundbreaking result will be a pass-no-pass phase diagram that shows under which conditions cancer cells can or cannot pass a vessel wall.
We will develop an innovative microfluidic platform with a multi-chip architecture for in vitro intravasation testing. In the individual chips we will create blood vessels with varying geometry and permeability, surrounded by extracellular matrices with pre-determined mechanical properties in which different tumor cells or cell clusters with known or controlled mechanical properties will be integrated. We will directly observe the intravasation process using live microscopy.
Our platform will open new approaches to cancer research; our discoveries will expand our scientific knowledge of metastasis. Beyond Intrap, the obtained insights can contribute to the development of highly needed novel cancer treatments that intervene with mechanical properties of cancer cells, matrix or blood vessels.