Stochastic phenotypic interconversion in tumors can generate heterogeneity

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• 作者：Giuseppina Simone
• 关键词：Heterogeneity ; Phenotype ; Galectin ; Tumor ; Stochastic Markov model
• 刊名：European Biophysics Journal
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：46
• 期：2
• 页码：189-194
• 全文大小：
• 刊物类别：Physics and Astronomy
• 刊物主题：Biochemistry, general; Biological and Medical Physics, Biophysics; Cell Biology; Neurobiology; Membrane Biology; Nanotechnology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1017
• 卷排序：46

文摘

Phenotype variations define heterogeneity in biological and molecular systems, and play a crucial mechanistic role, and heterogeneity has been demonstrated in tumor cells. In this work, cells from blood of patients affected by colon cancer were analyzed and sorted using a microfluidic assay based on galactose-active moieties and incubated for culturing in severe combined immunodeficiency (SCID) mice. Based on the results of these experiments, a model based on Markov theory is implemented and discussed to explain the equilibrium existing between phenotypes of cell subpopulations sorted using the microfluidic assay. In combination with the experimental results, the model has many implications for tumor heterogeneity; For example, it displays interconversion of phenotypes, confirming the experiments. Such interconversion generates metastatic cells and implies that targeting circulating tumor cells (CTC) will not be an efficient method for prevention of tumor recurrence. Most importantly, understanding the transitions between cell phenotypes in the cell population can improve understanding of tumor generation and growth.