Mechanic adaptability of metastatic cells in colon cancer

Abstract

Tumour microenvironment contributes importantly to the phenotype development of cancer cells, which receive and adapt to chemical and physical signals. It is hypothesized that remodelling of the actin cytoskeleton may enable tumor cells to evade normal apoptotic signalling and permit the acquisition of metastatic properties such as anchorage-independent growth and enhanced cell migration. Among different cancer cell lines, the SW480 and SW620 colon cells, derived from the same patient at different stages of tumour progression, represent a unique model to study the changes in mechanical properties during metastases. The SW480 derive from a primary colon tumour, while the SW620 originate from a population of malignant cells appeared in a lymph node metastases months after the initial surgery. In this work we measured by AFM, combined with Electron and Confocal Microscopy, the mechanic adaptability of cancer cell which reached in vivo the lymph node environment. We demonstrate how to resist to apoptotic stimuli in the lymphatic circulation, where the flow shear stress reduce cell survival, the metastatic cell increase their non-specific adhesion while retaining a flexible and soft cytoskeleton, related to uncontrolled growth properties. These features allow accomplishing the spreading in the circulation aim of metastatic cells.