The Universal Dynamics of Tumor Growth

Abstract

Scaling techniques were used to analyze the fractal nature of colonies of 15 cell lines growing in vitro as well as of 16 types of tumor developing in vivo. All cell colonies were found to exhibit exactly the same growth dynamics-which correspond to the molecular beam epitaxy (MBE) universality class. MBE dynamics are characterized by 1), a linear growth rate, 2), the constraint of cell proliferation to the colony/tumor border, and 3), surface diffusion of cells at the growing edge. These characteristics were experimentally verified in the studied colonies. That these should show MBE dynamics is in strong contrast with the currently established concept of tumor growth: the kinetics of this type of proliferation rules out exponential or Gompertzian growth. Rather, a clear linear growth regime is followed. The importance of new cell movements-cell diffusion at the tumor border-lies in the fact that tumor growth must be conceived as a competition for space between the tumor and the host, and not for nutrients or other factors. Strong experimental evidence is presented for 16 types of tumor, the growth of which cell surface diffusion may be the main mechanism responsible in vivo. These results explain most of the clinical and biological features of colonies and tumors, offer new theoretical frameworks, and challenge the wisdom of some current clinical strategies.

Migration rules: tumours are conglomerates of self-metastases

“…We start the simulations with a single cancer stem cell with unlimited replicative potential r ¼ N placed at the centre of the domain (the lattice point 175 rows down, 175 columns across). To accommodate the known limitation on cancer cell growth imposed by space constraints (Brú et al, 2003;Drasdo and Höhme, 2005;Galle et al, 2009), if all eight adjacent lattice points are occupied, a cell is considered inhibited and sent into quiescence until neighbouring space becomes available. Similar computational assumptions were made in a recent in silico model of opportunistic preneoplastic lesion growth driven by the death of adjacent normal stem cells (Chao et al, 2008).…”

“…The nature of this limitation has been debated, given the observation that tumour cells can push their neighbours under certain circumstances. However, as studied by Brú et al (2003) and confirmed by Drasdo and Höhme (2005), this ability is confined to a thin layer of cells near the surface of tumours and even to a thin ring of cells at the outer edge of wellnourished confluent tumour cell populations in vitro. Cells deeper in the tumours are limited by the surrounding cell mass.…”

“…One population-level factor limiting tumour progression is the space to grow (Brú et al, 2003;Pardal et al, 2003;Drasdo and Höhme, 2005;Chao et al, 2008). The nature of this limitation has been debated, given the observation that tumour cells can push their neighbours under certain circumstances.…”

Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media

“…This is a matter of interest in processes involved in wound healing or malignant tumor growth [1,2]. One of these procedures is based upon the dynamic scaling analysis (DSA) of colony fronts [3][4][5][6][7][8][9][10][11][12]. In this approach, the two-dimensional (2D) cell colony front dynamics is characterized through a set of dynamic scaling exponents (α, β, z, the roughness, the growth, and the dynamic exponents, respectively) derived from DSA applied to the colony front profiles and by comparing them with those expected from different complex statistical models [13,14].…”

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters

“…By referring to previous studies that described the active proliferation and angiogenesis in tumor border, the outer one‐third of the tumor area was assigned as periphery and the other area as the center 12, 13. After drawing the ROI covering the entire tumor areas, the radiologist drew another ROI that passed through two‐thirds of the tumor radius.…”