Apoptosis, cell adhesion and the extracellular matrix in the three-dimensional growth of multicellular tumor spheroids

In the last few years, it has become increasingly apparent that cell surviv al and death, especially apoptosis, strongly depend on cell adhesion and th e extracellular matrix, in addition, it has also become clear that the use of three-dimensional multicellular tumor spheroids, which mimick more close ly solid tumors in vivo, are a realistic experimental model to investigate many aspects of tumor biology. In the present review, after a general overv iew of the current knowledge regarding apoptosis, cell adhesion and the ext racellular matrix, the results obtained utilizing multicellular tumor spher oids in these types of studies are discussed. The main conclusion that may be drawn from a synthesis of the literature on these topics is that investi gations with multicellular tumor spheroids yield much useful-information th at is sometimes in contradiction to that obtained with monolayer cultures, but is closer to that derived from in vivo studies. Consequently, the autho rs encourage that these three-dimensional systems be used in many studies i n which cell death and adhesion are being examined. (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.