Cellular Adhesion - A Key Mechanism for Compartmentalization and Tumor Spreading?

Abstract

Motivated by the success of a novel surgical method taking account of cellular confinement to compartments to resect cervical cancer [1], the impact of compartmentalization on tumor development and spreading comes more and more into focus of today's cancer research [2].Compartmentalization is a universal and fundamental organization process in which in vivo different cell populations develop in separate confined areas. It has been observed that even tumor cells are confined to their original compartment for a relatively long time before they finally become able to overcome lineage boundaries.For that reason, the understanding of the mechanical principles underlying this process is of great importance. The differential adhesion hypothesis gives a first explanation by differences in surface tension and adhesiveness of the interacting cells [3]. In this context, we are investigating whether cellular adhesion is in fact a necessary or even sufficient factor to characterize compartmentalization and tumor spreading.For our studies, we use various cell types, such as healthy and cancerous breast cell lines of different malignancy as well as primary cells from human brain, breast, and cervix carcinoma. A set of different techniques is applied to characterize their mechanical properties and interactions: Cell-cell-adhesion forces are directly measured with a modified atomic force microscope. The Optical Stretcher is used for whole cell rheology. In complementary in vitro experiments, the process of cell aggregation and segregation is studied, employing a newly developed setup for long-term observation of droplet cultures. The combination of these techniques will help to shed some new light on the role of cellular adhesion for compartmentalization.[1] Hockel, Horn et al., Lancet Oncology 10 (7): 683-692 (2009).[2] Fritsch et al., Nature Physics 6 (10): 730-732 (2010).[3] Foty, Steinberg, Dev. Biol. 278 (1): 255-263 (2005).