TY - JOUR
T1 - Pattern of self-organization in tumour systems
T2 - Complex growth dynamics in a novel brain tumour spheroid model
AU - Deisboeck, T. S.
AU - Berens, M. E.
AU - Kansal, A. R.
AU - Torquato, S.
AU - Stemmer-Rachamimov, A. O.
AU - Chiocca, E. A.
PY - 2001
Y1 - 2001
N2 - We propose that a highly malignant brain tumour is an opportunistic, self-organizing and adaptive complex dynamic biosystem rather than an unorganized cell mass. To test the hypothesis of related key behaviour such as cell proliferation and invasion, we have developed a new in vitro assay capable of displaying several of the dynamic features of this multiparameter system in the same experimental setting. This assay investigates the development of multicellular U87MGmEGFR spheroids in a specific extracellular matrix gel over time. The results show that key features such as volumetric growth and cell invasion can be analysed in the same setting over 144 h without continuously supplementing additional nutrition. Moreover, tumour proliferation and invasion are closely correlated and both key features establish a distinct ratio over time to achieve maximum cell velocity and to maintain the system's temporo-spatial expansion dynamics. Single cell invasion follows a chain-like pattern leading to the new concept of a intrabranch homotype attraction. Since preliminary studies demonstrate that heterotype attraction can specifically direct and accelerate the emerging invasive network, we further introduce the concept of least resistance, most permission and highest attraction as an essential principle for tumour invasion. Together, these results support the hypothesis of a self-organizing adaptive biosystem.
AB - We propose that a highly malignant brain tumour is an opportunistic, self-organizing and adaptive complex dynamic biosystem rather than an unorganized cell mass. To test the hypothesis of related key behaviour such as cell proliferation and invasion, we have developed a new in vitro assay capable of displaying several of the dynamic features of this multiparameter system in the same experimental setting. This assay investigates the development of multicellular U87MGmEGFR spheroids in a specific extracellular matrix gel over time. The results show that key features such as volumetric growth and cell invasion can be analysed in the same setting over 144 h without continuously supplementing additional nutrition. Moreover, tumour proliferation and invasion are closely correlated and both key features establish a distinct ratio over time to achieve maximum cell velocity and to maintain the system's temporo-spatial expansion dynamics. Single cell invasion follows a chain-like pattern leading to the new concept of a intrabranch homotype attraction. Since preliminary studies demonstrate that heterotype attraction can specifically direct and accelerate the emerging invasive network, we further introduce the concept of least resistance, most permission and highest attraction as an essential principle for tumour invasion. Together, these results support the hypothesis of a self-organizing adaptive biosystem.
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U2 - 10.1046/j.1365-2184.2001.00202.x
DO - 10.1046/j.1365-2184.2001.00202.x
M3 - Article
C2 - 11348426
AN - SCOPUS:0035030266
SN - 0960-7722
VL - 34
SP - 115
EP - 134
JO - Cell and Tissue Kinetics
JF - Cell and Tissue Kinetics
IS - 2
ER -