Rheology Reveals Pro-metastatic Lung Stiffening Following Exposure to Tumor-derived Microparticles

Tumor cells have been shown to respond to chemotherapy by shedding increased numbers of tumor-derived microparticles (TMPs). These TMPs have been shown to affect the tumor microenvironment and support tumor growth. We propose that TMPS also induce changes in the mechanostructure of pre-metastatic sites to promote and support tumor cell seeding. Thus, we have evaluated the effects of TMPs shed from breast cancer cells on the metastatic propensity of tumors towards the lungs and correlated that with changes in the lung mechanics. Specifically, the mechanics of lung-slices from mice injected with TMPs that were shed from cancer cells exposed to paclitaxel or TMPs from untreated cancer cells were compared to untreated lung using a shear rheometer. We observe that lung slices are viscoelastic with mucus-like rheology, and reveal local stiffening in paclitaxel exposed conditions compared to control conditions. Thus, chemotherapy-induced TMPs stimulate a survival-driven response modifying pre-metastatic sites, which may lead to tumor spreading and metastasis.