scholarly journals Asymmetric Binomial Statistics Explains Organelle Partitioning Variance in Cancer Cell Proliferation

2021 ◽  
Author(s):  
Giovanna Peruzzi ◽  
Mattia Miotto ◽  
Roberta Maggio ◽  
Giancarlo Ruocco ◽  
Giorgio Gosti

ABSTRACTAsymmetric inheritance of organelle and cellular compounds between daughter cells impacts on the phenotypic variability and was found to be a hallmark for differentiation and rejuvenation in stem-like cells as much as a mechanism for enhancing resistance in bacteria populations. Whether the same processes take place in the context of cancer cell lines is still poorly investigated. Here, we present a method that allows the measurement of asymmetric organelle partitioning, and we use it to simultaneously measure the partitioning of three kinds of cellular elements, i.e. cytoplasm, membrane, and mitochondria in a proliferating population of human Jurkat T-cells. For this porpoise, we use multiple live cell markers which permit us both to follow the partitioning process for multiple generations and to investigate the correlations between the partitioning of different cellular constituents. Assuming a minimal model of asymmetric partitioning where cell sub-components are divided according to a biased binomial statistics, we derived exact analytical relationships for the average fluorescence intensity and its fluctuations as a function of the generation, obtaining an excellent agreement with the experimental measurements.We found that although cell cytoplasm is divided symmetrically, mitochondria and membrane lipids are asymmetrically distributed between the two daughter cells and present a stable positive correlation with cytoplasm apportioning, which is incompatible with an independent division mechanism. Therefore, our findings show that asymmetric segregation mechanisms can also arise in cancer cell populations, and that, in this case, membrane lipids and mitochondria do not respectively segregate independently from the cytoplasm. This helps us understand the high phenotypic variability reported in these cancer cell lines. In perspective, this could be particularly relevant in the case of tumor micro-environment diversity, where comprehension of the non-genetic cell heterogeneity could pave the way to novel and more targeted therapies. Moreover, the developed experimental and theoretical apparatus can be easily generalized to different cell kinds and different cell sub-components providing a powerful tool for understanding partitioning-driven heterogeneity.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2571-2571
Author(s):  
Cosette Zacarias ◽  
Vijaya Satish Sekhar Pilli ◽  
William E. Plautz ◽  
A'drianne Wells ◽  
Rinku Majumder

Abstract Introduction: Procoagulants such as Factor IX and thrombin play major roles in cancer cell proliferation and migration; however, a role for anticoagulant proteins in cancer biology has not been elucidated. The anticoagulant Protein S (PS), its homologous protein Growth Arrest Specific protein-6 (GAS-6), and the receptors for these proteins, Tyro-3, Axl and Mertk (TAM), are over expressed in many cancer cells. TAM family receptors regulate functions such as cell survival, proliferation, migration, and apoptosis. The consequences of activation of each of these receptors varies, although the mechanism that leads to different outcomes is unknown. We hypothesized that the PS and GAS-6 ligands are responsible for the variations in the functions of these signaling cascades. Methods: We used qPCR to analyze the pancreatic cancer cell lines Miapaca-2 and Panc-1 for variations in the expression of GAS-6 and PS. We sequestered PS and GAS-6 with antibodies and used FACS analysis to detect effects on the cell cycle and on cell cycle regulators. Results: GAS-6 was observed to be highly expressed in proliferating Miapaca-2 cells compared with Panc-1 cells, whereas there was no significant difference in PS mRNA levels between these cell lines. For the cell line Miapaca-2, antibody sequestration of GAS-6 arrested the cell cycle in S-phase and increased p53 phosphorylation; conversely, inhibition of PS reduced p53 phosphorylation. Conclusion: Our results indicate that PS and GAS-6 act antagonistically in controlling pancreatic cancer cell proliferation, and we hypothesize that the ratio of GAS-6 to PS expression is key to this regulation. We will further confirm our hypothesis by overexpressing and knocking down PS and GAS-6 in the pancreatic cancer cell lines. Disclosures No relevant conflicts of interest to declare.


2007 ◽  
Vol 7 (2) ◽  
pp. 69
Author(s):  
Sung Su Park ◽  
Jin-Woo Park ◽  
Jae-Woon Choi ◽  
Lee-Chan Jang ◽  
Sung-Il Woo ◽  
...  

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanna Peruzzi ◽  
Mattia Miotto ◽  
Roberta Maggio ◽  
Giancarlo Ruocco ◽  
Giorgio Gosti

AbstractAsymmetric inheritance of organelles and compounds between daughter cells is considered a hallmark for differentiation and rejuvenation in stem-like and cancer cells, as much as a mechanism for enhancing resistance in bacteria populations. In non-differentiating homogeneous cancer cells, asymmetric division is still poorly investigated. Here, we present a method based on the binomial partitioning process that allows the measurement of asymmetric organelle partitioning with multiple live cell markers without genetically mutating the cells. We demonstrate our method by measuring simultaneously the partitioning of three cellular elements, i.e., cytoplasm, membrane, and mitochondria in human Jurkat T-cells. We found that although cell cytoplasm is partitioned symmetrically, mitochondria and membrane lipids are asymmetrically partitioned between daughter cells. Moreover, we observe that mitochondria and membrane lipids present a stable positive correlation with cytoplasm, incompatibly with a binomial partition mechanism produced by two independent partitioning processes. Our experimental apparatus, combined with our theoretical framework, could be generalized to different cell kinds, providing a tool for understanding partitioning-driven biological processes.


2006 ◽  
Vol 175 (4S) ◽  
pp. 258-258
Author(s):  
Ruth Schwaninger ◽  
Cyrill A. Rentsch ◽  
Antoinette Wetterwald ◽  
Irena Klima ◽  
Gabri Van der Pluijm ◽  
...  

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