Invited Talk

Understanding and exploiting cancer cell adhesion

University of California, San Diego Sanford Consortium for Regenerative Medicine La Jolla, CA USA

Contact:  | Website

Metastasis significantly reduces cancer patient survival rates. Although evidence exists that only a fraction of tumor cells contribute to metastatic disease, no prognostic biomarkers currently exist to identify these cells. Here, I will present the discovery of a physical marker that predicts both metastatic potential and survival rates. Cells disseminating from mammary tumors are weakly adherent, and when presorted by adhesion, primary tumors created from strongly adherent cells exhibit fewer lung metastases than weakly adherent cells or unsorted populations. Admixed cancer lines can be separated by label-free adhesive signatures using a next-generation flow chamber. When applied to metastatic tumors, the chamber retrospectively predicted metastatic disease from stromal samples with 100% specificity, 85% sensitivity, and AUC of 0.94. The chamber can also differentiate more weakly adherent metastatic mammary tumors from patients versus their contralateral control tissue obtained via mastectomy. Mechanistically, weakly adherent cells largely ignore the gradient that exists as one migrates away from stiff tumors, i.e. adurotax. Biophysical modeling and experimental validation suggest that differences in cell migration and durotaxis between weakly and strongly adherent cells are driven by differences in intra-cellular actomyosin activity. These results together suggest how, unlike other senescent cells, metastatic cancer cells use weak adhesion to navigate against stiffness gradients and how we can use this to our advantage to assess metastatic potential of patient tumors.