Rigid tumors contain soft cancer cells

Palpation, as already mentioned in the ancient Egyptian medical text Ebers Papyrus, utilizes that solid tumors are stiffer than the surrounding tissue. However, cancer cell lines tend to soften, which may intuitively foster invasion by enhancing the ability of cancer cells to squeeze through dense tissue. This paradox raises questions besides the oxymoron itself: Does softness emerge from adaptation to the external microenvironment? Or are soft cells already present inside a rigid primary tumor mass to support cancer cell unjamming? We investigate primary tumor explants from patients with breast and cervix carcinomas on multiple length scales from the tissue level down to single cells. We find that primary tumors are highly heterogeneous in their mechanical properties. From the tissue level this heterogeneity persists down to the scale of individual cells in cancer cell clusters, resulting in a broad distribution of cell rigidities with a higher fraction of softer, more squeezable cells. Plus, squeezed cell shapes correlate with cancer cell motility. Mechanical modelling based on patient data reveals that a tumor mass as a whole is able to maintain a rigid, solid behavior even when it contains a significant fraction of very soft cells. Cell softening induced cancer cell unjamming generates heterogeneous cancer cell clusters with a solid backbone of rigid cells surrounded by soft motile cells.