Which Chemotherapy Drugs Alter Cell Mechanical Properties with Impact on Metastasis?

We recently showed that Doxorubicin and Daunorubicin, commonly used anti-cancer drugs, stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. We are taking further steps to find out which other anti-cancer drugs might have similar effects. We treat myelocytic (HL60), myelogenous (K562) and lymphocytic (Jurkat) leukemic cancer cells with the drugs Nocodazole, Paclitaxel, Imatinib, Lenalidomide and Hydroxyurea, and then measure their mechanical properties using the microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation (pulmonary microcirculation) and enables the measurement of cell mechanical properties via transit times through the device. We also measure the migration of cells thus treated to determine the functional relevance of the MMM results. Preliminary results from MMM measurements show that Paclitaxel and Nocodazole treated HL60/K56 cells exhibit significantly altered transit times. Other results will be presented. It is already known that Nocodazole and Paclitaxel target microtubules and cell division. However, microtubules along with F-actin and intermediate filaments, determine cell mechanical properties. This work might be an important contribution to the new research frontier called Physics of Cancer, which focuses on the mechanical properties of cancer cells and their role in cancer progression and metastasis. Specifically, it suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies since it is metastasis that accounts for over 90% of cancer-related deaths.