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 sphero id-based studies which have defined a role for intercellular adhesion in di ctating cellular fate. Critical roles for adhesion molecules, such as the i ntegrin and cadherin families, have been established. In addition, it appea rs that components of the signaling pathways that control cellular prolifer ation may also influence the cellular decision to live or die. Further comp lexity arises from the action of soluble factors, like epidermal growth fac tor, and three-dimensional culture systems are providing insights into how integration of these multiple signals is achieved. Given that cellular adhe sion 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 discus sed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.