scholarly journals Asymmetric binomial statistics explains organelle partitioning variance in cancer cell proliferation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanna Peruzzi ◽  
Mattia Miotto ◽  
Roberta Maggio ◽  
Giancarlo Ruocco ◽  
Giorgio Gosti
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Membrane Lipids ◽  
Cancer Cell Proliferation ◽  
Biological Processes ◽  
Cell Cytoplasm ◽  
Jurkat T Cells ◽  
Daughter Cells ◽  
Experimental Apparatus ◽  
Binomial Statistics

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.

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
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Membrane Lipids ◽  
Phenotypic Variability ◽  
Cancer Cell Lines ◽  
Cancer Cell Proliferation ◽  
Daughter Cells ◽  
Asymmetric Partitioning ◽  
Asymmetrically Distributed ◽  
Binomial Statistics

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.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

2011 ◽  
Vol 108 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Mu Yao ◽  
Chanlu Xie ◽  
Maryrose Constantine ◽  
Sheng Hua ◽  
Brett D. Hambly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
East Asia ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Prostate Cancer Cells ◽  
The Mediterranean

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

scholarly journals Gestational Tissue-Derived Human Mesenchymal Stem Cells Use Distinct Combinations of Bioactive Molecules to Suppress the Proliferation of Human Hepatoblastoma and Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Nitchapon Paiboon ◽  
Witchayaporn Kamprom ◽  
Sirikul Manochantr ◽  
Chairat Tantrawatpan ◽  
Duangrat Tantikanlayaporn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Mesenchymal Stem Cells ◽  
Bioactive Molecules ◽  
Mass Spectrometry Analysis ◽  
Cancer Cell Proliferation ◽  
Protein Fractionation ◽  
Spectrometry Analysis ◽  
Colorectal Cancer Cells

Background. Cancer has been considered a serious global health problem and a leading cause of morbidity and mortality worldwide. Despite recent advances in cancer therapy, treatments of advance stage cancers are mostly ineffective resulting in poor survival of patients. Recent evidences suggest that multipotent human mesenchymal stem cells (hMSCs) play important roles in growth and metastasis of several cancers by enhancing their engraftment and inducing tumor neovascularization. However, the effect of hMSCs on cancer cells is still controversial because there are also evidences demonstrating that hMSCs inhibited growth and metastasis of some cancers. Methods. In this study, we investigated the effects of bioactive molecules released from bone marrow and gestational tissue-derived hMSCs on the proliferation of various human cancer cells, including C3A, HT29, A549, Saos-2, and U251. We also characterized the hMSC-derived factors that inhibit cancer cell proliferation by protein fractionation and mass spectrometry analysis. Results. We herein make a direct comparison and show that the effects of hMSCs on cancer cell proliferation and migration depend on both hMSC sources and cancer cell types and cancer-derived bioactive molecules did not affect the cancer suppressive capacity of hMSCs. Moreover, hMSCs use distinct combination of bioactive molecules to suppress the proliferation of human hepatoblastoma and colorectal cancer cells. Using protein fractionation and mass spectrometry analysis, we have identified several novel hMSC-derived factors that might be able to suppress cancer cell proliferation. Conclusion. We believe that the procedure developed in this study could be used to discover other therapeutically useful molecules released by various hMSC sources for a future in vivo study.

scholarly journals The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricardo Romero-Moreno ◽  
Kimberly J. Curtis ◽  
Thomas R. Coughlin ◽  
Maria Cristina Miranda-Vergara ◽  
Shourik Dutta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ex Vivo ◽  
Metastatic Cancer ◽  
Culture Method ◽  
Cancer Cell Proliferation ◽  
Promote Breast Cancer

Abstract Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through the vasculature and invade new tissues can remain in a non-proliferative dormant state for years before colonizing the metastatic site. Switching from dormancy to colonization is the rate-limiting step of bone metastasis. Here we develop an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identifies the chemokine CXCL5 as a candidate to induce metastatic colonization. Additional studies using CXCL5 recombinant protein suggest that CXCL5 is sufficient to promote breast cancer cell proliferation and colonization in bone, while inhibition of its receptor CXCR2 with an antagonist blocks proliferation of metastatic cancer cells. This study suggests that CXCL5 and CXCR2 inhibitors may have efficacy in treating metastatic bone tumors dependent on the CXCL5/CXCR2 axis.

Development of a novel method for the bioanalysis of benfotiamine and sulbutiamine in cancer cells

2016 ◽  
Vol 8 (28) ◽  
pp. 5596-5603 ◽  
Author(s):  
Jaeah Kim ◽  
Christopher P. Hopper ◽  
Kelsey H. Connell ◽  
Parisa Darkhal ◽  
Jason A. Zastre ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Biological Samples ◽  
Cancer Cell Proliferation ◽  
Essential Step ◽  
Novel Method

Quantification of benfotiamine and sulbutiamine, synthetic thiamine analogs, in biological samples is an essential step toward understanding the role of these thiamine analogs on cancer cell proliferation.

scholarly journals PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengbin Chai ◽  
Li Wang ◽  
Yabing Zheng ◽  
Na Liang ◽  
Xiwei Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Expression Pattern ◽  
Colony Formation ◽  
Regulatory Mechanism ◽  
Cancer Cell Proliferation ◽  
Colon Cancer Cells ◽  
Cancer Tissues

Abstract Background CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. Methods Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. Results CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. Conclusions PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

scholarly journals The importance of serine metabolism in cancer

2016 ◽  
Vol 214 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Katherine R. Mattaini ◽  
Mark R. Sullivan ◽  
Matthew G. Vander Heiden
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Cancer Cells ◽  
De Novo ◽  
Redox Homeostasis ◽  
Cancer Cell Proliferation ◽  
Acid Transport ◽  
Nucleotide Synthesis ◽  
Serine Metabolism

Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer.

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