Poster

Shape and Density Reveal Prognostic Relevance of Potentially Motile Breast Cancer Cells

Pablo Gottheil¹, Jürgen Lippoldt¹, Steffen Grosser¹, Hans Kubitschke¹, Frédéric Renner¹, Mohamad Saibah¹, Dimitrij Tschodu¹, Michael Höckel², Benjamin Wolf², Bahriye Aktas², Axel Niendorf³, Josef Käs¹

Contact: 

Distant metastasis is an important and, in most cases, a lethal hallmark of cancer. Due to a lack of suitable biological markers, cancer cell motility as a prerequisite of the metastatic process has a negligible impact on the current clinical diagnosis. Cell unjamming that occurs in embryonic development and diseases such as cancer can provide a physical marker to solve this problem.
Via vital cell tracking and segmentation in patient-derived tumor explants, we derived a soft matter physics-based marker that detects the ability of cells to move in static histological images via cell and nucleus shapes and densities. Previously, cell shapes and densities have been used separately to describe the unjamming transition. Moreover, the role of the nucleus is not considered in the current unjamming models.
We conducted an exploratory retrospective histopathological study. With two independent breast cancer patient collectives, we train (N=688) and validate (N=692, log-rank p = 0.002) an empirical decision boundary in the space of ensemble cell and nucleus shapes as well as nucleus number density in order to identify a patient’s risk of developing distant metastases. Patients with high metastatic risk are localized in the region of the parameter space characterized by low densities and/or elongated cell and nucleus shapes, likely representing a more unjammed state.
We conclude that cancer cell unjamming within primary tumors as an emergent physical phenomenon is part of the metastatic cascade and may help refine the diagnosis.