Abstract
There is a constant need of features able to characterize potentially metastatic cells among the heterogeneous cell subpopulations which constitute a tumor. Image cytometry of metastatic tumor cells give rise to variable results, partly because of a heterogeneous origin of cells, or potential drug effects. The aim of this work was to characterize nuclear changes observed in metastatic cell clones issued in vitro from the same parental cell population The nuclear phenotypes of 6 cell sublines isolated from a rat rhabdomyosarcoma cell line and differing in their metastatic ability were evaluated by image cytometry on Feulgen‐stained preparations. Densitometric [5], geometric [3] and textural [9] features were computed from each nuclear image. For each cell subline, a metastatic score, ranging from 0 to 10, was calculated on the basis of in vitro invasivity data, by measuring the number of pulmonary metastases observed after s.c. graft of tumor cells in rats. Data obtained were compared to karyotype, growth characteristics, and oncogene expressions of cell lines. The nuclear DNA content, the chromosome numbers, the cell sublines doubling times, and the distribution of cells within the cell cycle appear unrelated with this score. On the contrary, increase in metastatic ability is accompanied by changes in chromatin pattern as assessed by textural features. Progressive increase in chromatin condensation can be observed in cell sublines with increasing metastatic score. These results were confirmed by an unsupervised multivariate partitioning of rhabdomyosarcoma cells which identified two separate subsets whose distributions within the analyzed cell lines correlate with their metastatic ability. These data suggest that, in rat rhabdomyosarcoma cell sublines, metastatic ability could be associated with nuclear morphological changes at the level of chromatin texture.
Highlights
In spite of significant improvements both in diagnosis and therapy, many deaths in cancer patients are due to metastases
A major advance in this field of metastasis research has come from the isolation of tumor cell subpopulations that display markedly different metastatic behavior
Since rat rhabdomyosarcoma cell sublines with low and high metastatic potential have been described and characterized for their biochemical and invasive properties, and oncogenes expression [18,19,36], the aim of this work was to evaluate by image analysis the DNA content and nuclear structure of these cell sublines in order to identify possible changes in chromatin organization related to the metastatic potential of these cells
Summary
In spite of significant improvements both in diagnosis and therapy, many deaths in cancer patients are due to metastases. There is a constant need of features able to characterize potentially metastatic cells among the heterogeneous cell subpopulations which constitute a tumor [7,10,37,38]. A major advance in this field of metastasis research has come from the isolation of tumor cell subpopulations that display markedly different metastatic behavior. Some of these cell subpopulations, obtained by selection or transfection, have been accurately described and characterized in terms of biochemical properties and invasive activity [1,34,36], but attempts to correlate the morphological features of these tumor cell sublines with their metastatic potential are scarce. In the context of metastatic potential, comparisons of mouse B16 melanoma cell lines revealed in highly metastatic variants an increased chromatin condensation [31], heterogeneity of DNA ploidy
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