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Study of Cancer Stem Cell Subpopulations in Breast Cancer Models

机译：Study of Cancer Stem Cell Subpopulations in Breast Cancer Models

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Abstract The heterogeneous nature of tumor populations and the presence of tumor stem cells is one of the causes for resistance of malignant neoplasms to anticancer therapies and emergence of recurrences and metastases as well as for complexities in the management of this pathology. The aim of this study was to enrich multicellular tumor spheroids (MCTSs) of the mammary adenocarcinoma MCF-7 line cells with cancer stem cells (CSCs) and study the obtained CSC subpopulation using biochemical, immunological, and cytological methods. The results of our study have shown that the percentage of CSCs within a population of multicellular tumor spheroids in a nutrient-depleted growth medium increases significantly with certain growth factor supplements. For example, the percentage of the cells expressing CD133 and Nestin increased, respectively, from 12.47 to 82.08% and from 31.3 to 82.58%. The data of immunocytochemical staining showed that the count of cells expressing the CSC markers, such as CD44, CD133, and bmi1, also increased. The aldehyde dehydrogenase activity reached 0.07 mol/mg protein per min in the MCF7 line cells under the monolayer growth conditions and increased up to 1.58 mol/mg protein per min in CSCs-enriched multicellular tumor spheroids (eMCTSs). The activity of glucose-6-phosphate dehydrogenase (G6PDH) in the tumor cells was 934.6 ± 148.3 × 10–6 mol/mg protein per min under the monolayer growth conditions and increased more than 1.5 times with enriching MCTSs with CSCs. The activity of lactate dehydrogenase (LDH) in MCF-7 cells was 65.12 ± 1.28 μmol/mg protein per min under the monolayer growth conditions and decreased by 5.5 times due to a growth in the CTCs-enriched MCTSs. Thus, based on the authors’ data, one can assume that the MCF-7 receptor and energy profile change due to enriching a tumor cell population with CSCs under growth conditions, thus bringing the CTCs-enriched spheroids closer to the characteristics of metastatic micronodules and the tumor cells to those of cancer stem cells.

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