Oscillations in growth of multicellular tumour spheroids: a revisited quantitative analysis

Abstract

Multicellular tumour spheroids (MTS) provide an important tool for study of the microscopic properties of solid tumours and their responses to therapy. Thus, observation of large-scale volume oscillations in MTS, reported several years ago by two independent groups (1,2), in our opinion represent a remarkable discovery, particularly if this could promote careful investigation of the possible occurrence of volume oscillations of tumours 'in vivo'. Because of high background noise, quantitative analysis of properties of observed oscillations has not been possible in previous studies. Such an analysis can be now performed, thanks to a recently proposed approach, based on formalism of phenomenological universalities (PUN). Results have provided unambiguous confirmation of the existence of MTS volume oscillations, and quantitative evaluation of their properties, for two tumour cell lines. Proof is based not only on quality of fitting of the experimental datasets, but also on determination of well-defined values of frequency and amplitude of the oscillations for each line investigated, which would not be consistent with random fluctuation. Biological mechanisms, which can be directly responsible for observed oscillations, are proposed, which relates also to recent work on related topics. Further investigations, both at experimental and at modelling levels, are also suggested. Finally, from a methodological point of view, results obtained represent further confirmation of applicability and usefulness of the PUN approach.