Poster

Migratory based local cancer cell invasion

Dipanwita Dutta, Josef A. Käs

University of Leipzig, Faculty of Physics and Earth System Sciences, Soft Matter Physics Division, Leipzig, Germany

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Invasion of cancer cells is a critical intermediate step of metastasis formation. After escaping from the primary tumor, the cancer cells spread in the immediate surrounding extracellular matrix. In the next steps, the cancer cells enter into the blood vessel, circulate with the blood flow, come out of the blood vessel at secondary sites and form secondary tumors. Throughout this process, the cancer cells must translocate through the meshwork of the extracellular matrix and cross tissue boundaries, collectively known as invasion. While there has been substantial research on cancer cell invasion in the ECM, there is limited understanding of how cancer cells invade other cell clusters or cell layers. Moreover, the existing studies with the invasion assays do not incorporate live measurement of the invasion mechanism. However, since invasion is a specialized form of migration, and migration is inherently dynamic, the lack of live observations has hindered the understanding of the physics behind the invasion mechanism of cancer cells into other cell clusters.

To address this gap, I have conducted live-cell imaging experiments to observe cancer cells as they invade other cell clusters and layers in real time. I will present these experiments in this poster along with the preliminary observations. Although the live observation of the invasion mechanism poses significant challenges, the experiments have yielded promising preliminary results. Remarkably, cancer cells do not apply any brute force to break the cell layers to move. Instead, they exhibit continuous fluctuations, searching for available spaces and dynamically reshaping themselves which suggests a more strategic, adaptive form of movement. Moreover, it seems that the cancer cells readily attach to other cell clusters but do not invade immediately. This points to a complex interaction between cells and their surrounding environment during the invasion process which is not easily triggered.

Intriguingly, even when the cancer cells move constantly within a cluster, they do not cross boundaries when encountering another cluster of same cell type indicating that an active regulatory mechanism may be involved. Our hypothesis is that the cancer cells employ Brownian Ratchet mechanism to facilitate invasion into cell layers, with non-equilibrium thermodynamics playing a crucial role. All these observations provide a new perspective on how cancer cells navigate physical barriers and the possible mechanisms to overcome these challenges during metastasis.