Gompertzian growth pattern correlated with phenotypic organization of colon carcinoma, malignant glioma and non‐small cell lung carcinoma cell lines

Abstract

In the current study we present a Gompertzian model for cell growth as a function of cell phenotype using six human tumour cell lines (A-549, NCI-H596, NCI-H520, HT-29, SW-620 and U-251). Monolayer cells in exponential growth at various densities were quantified over a week by sulforhodamine B staining assay to produce cell-growth curves. A Gompertz equation was fitted to experimental data to obtain, for each cell line, three empirical growth parameters (initial cell density, cell-growth rate and carrying capacity - the maximal cell density). A cell-shape parameter named deformation coefficient D (a morphological relationship among spreading and confluent cells) was established and compared by regression analysis with the relative growth rate parameter K described by the Gompertz equation. We have found that coefficient D is directly proportional to the growth parameter K. The fit curve significantly matches the empirical data (P < 0.05), with a correlation coefficient of 0.9152. Therefore, a transformed Gompertzian growth function was obtained accordingly to D. The degree of correlation between the Gompertzian growth parameter and the coefficient D allows a new interpretation of the growth parameter K on the basis of morphological measurements of a set of tumour cell types, supporting the idea that cell-growth kinetics can be modulated by phenotypic organization of attached cells.

Retinol induces morphological alterations and proliferative focus formation through free radical-mediated activation of multiple signaling pathways

“…The other protein kinase inhibitors had no effect or caused new patterns of morphology modification in retinol-treated cells, such as observed for the p38 inhibitor SB203580 (10 µmol/L) and the Akt inhibitor LY294002 (10 µmol/L). To better understand how these morphological modifications were associated to malignant deformation, we calculated the deformation coefficient D (Figure 3B), a morphological relationship among spreading and confluent cells, related to cell malignancy, invasiveness and contact inhibition applied to cancer cell lines [24] . The coefficient D for cells treated with retinol for 24 h (D=2.812±0.229) was significantly lower than in control cells (D=5.258±0.538), indicating loss of substrate adhesion and contact inhibition [24] .…”

“…To better understand how these morphological modifications were associated to malignant deformation, we calculated the deformation coefficient D (Figure 3B), a morphological relationship among spreading and confluent cells, related to cell malignancy, invasiveness and contact inhibition applied to cancer cell lines [24] . The coefficient D for cells treated with retinol for 24 h (D=2.812±0.229) was significantly lower than in control cells (D=5.258±0.538), indicating loss of substrate adhesion and contact inhibition [24] . Besides Trolox, the p38 inhibitor SB203580 and the ERK1/2 inhibitor U0126 (10 µmol/L) also inhibited this effect, while other protein kinase inhibitors did not.…”

“…As cells become rounded, DNA synthesis gradually stops [48] ; inversely, most cells require spreading on extracellular matrix substrate for proper growth and normal function [49] . Such relationships among growth and shape have been studied by regression analysis and resulted in a cell deformation parameter -the deformation coefficient D, which describes the amplitude of cell shape variation, showing positive correlation with kinetic parameters of growth described by the Gompertz model [24] .…”

“…The increase in the difference between spread and confluent cells implies an increase of coefficient D [24] . Morphometrical measurements were obtained by analysis of the scanned phase-contrast photomicrographs of cells plated as dispersed and confluent densities.…”

5-Year Lung Cancer Screening Experience

“…3,4 Gompertzian growth is exponential at an early stage and approaches a plateau as the tumor size increases. 4 Most curves showed fairly steady linear or exponential increments of growth, but there also were curves that were close to horizontal and curves that showed accelerated, greater-than-exponential growth compared with earlier rates. It is possible that some cancers were resected prior to reaching the plateau phase described by Gompertzian growth.…”