Spheroids and cell survival.

In contrast to most traditional cell culture systems, spheroids represent a unique opportunity to recapitulate aspects of cell homeostasis and as such better reflect in vivo tumor biology. This review highlights recent spheroid-based studies which have defined a role for intercellular adhesion in dictating cellular fate. Critical roles for adhesion molecules, such as the integrin and cadherin families, have been established. In addition, it appears that components of the signaling pathways that control cellular proliferation may also influence the cellular decision to live or die. Further complexity arises from the action of soluble factors, like epidermal growth factor, and three-dimensional culture systems are providing insights into how integration of these multiple signals is achieved. Given that cellular adhesion may serve as a regulator of apoptosis, and in particular that correct receptor engagement can activate signaling pathways promoting cell survival, additional implications for our understanding of tumor biology are discussed.