miRNA Combinatorics and its Role in Cell State Control—A Probabilistic Approach

A hallmark of cancer evolution is that the tumor may change its cell identity and improve its survival and fitness. Drastic change in microRNA (miRNA) composition and quantities accompany such dynamic processes. Cancer samples are composed of cells’ mixtures of varying stages of cancerous progress. Therefore, cell-specific molecular profiling represents cellular averaging. In this study, we consider the degree to which altering miRNAs composition shifts cell behavior. We used COMICS, an iterative framework that simulates the stochastic events of miRNA-mRNA pairing, using a probabilistic approach. COMICS simulates the likelihood that cells change their transcriptome following many iterations (100 k). Results of COMICS from the human cell line (HeLa) confirmed that most genes are resistant to miRNA regulation. However, COMICS results suggest that the composition of the abundant miRNAs dictates the nature of the cells (across three cell lines) regardless of its actual mRNA steady-state. In silico perturbations of cell lines (i.e., by overexpressing miRNAs) allowed to classify genes according to their sensitivity and resilience to any combination of miRNA perturbations. Our results expose an overlooked quantitative dimension for a set of genes and miRNA regulation in living cells. The immediate implication is that even relatively modest overexpression of specific miRNAs may shift cell identity and impact cancer evolution.

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High Level Expression of Active Human Prothrombin in a Vaccina Virus Expression System

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656335 ◽

1992 ◽

Vol 68 (02) ◽

pp. 119-124 ◽

Cited By ~ 10

Author(s):

F G Falkner ◽

P L Turecek ◽

R T A MacGillivray ◽

W Bodemer ◽

F Scheiflinger ◽

...

Keyword(s):

Vaccinia Virus ◽

Cell Lines ◽

Expression System ◽

Human Cell Line ◽

Cell System ◽

Time Saving ◽

Expression Levels ◽

Mammalian Cell Lines ◽

Cell Line Hela ◽

Virus Expression

SummaryWe have worked out an efficient and time saving procedure for the expression of recombinant human prothrombin. The glycoprotein was expressed in the vaccinia virus expression system in several mammalian cell lines. The kidney cell lines Vero and BHK and the human cell line Hela were found to efficiently secrete prothrombin. Expression levels of 3–4 µg of factor II per 106 cells per day corresponding to 18–23 mU per 106 cells per day were achieved. Since the expression levels obtained with the vaccinia virus/Vero cell system were comparable to those obtained in amplified transformed CHO cells it provides an alternative system for the efficient expression of human prothrombin and may allow to further elucidate structure-function relationships of (pro)thrombin and its various effectors.

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The Extensive and Expensive Impacts of HEp-2 [HeLa], Intestine 407 [HeLa], and Other False Cell Lines in Journal Publications

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/24725552211051963 ◽

2021 ◽

pp. 247255522110519

Author(s):

Christopher T. Korch ◽

Amanda Capes-Davis

Keyword(s):

Cell Line ◽

Cell Lines ◽

Scientific Literature ◽

Cancer Cell Line ◽

Biomedical Literature ◽

Cervical Cancer Cell Line ◽

Original Culture ◽

Cell Line Hela ◽

Normal Intestine ◽

Line Hela

Cell lines are essential models for biomedical research. However, they have a common and important problem that needs to be addressed. Cell lines can be misidentified, meaning that they no longer correspond to the donor from whom the cells were first obtained. This problem may arise due to cross-contamination: the accidental introduction of cells from another culture. The contaminant, which is often a rapidly dividing cell line, will overgrow and replace the original culture. The end result is a false cell line, also known as a misidentified or imposter cell line. False cell lines may come from an entirely different species, tissue, or cell type than the original donor. If undetected, false cell lines produce unreliable and irreproducible results that pollute the biomedical literature and threaten the development of reliable drug discovery and meaningful patient treatments. The goal of this study was to ascertain how widespread this problem is and how it affects the literature, as well as to estimate how much funding has been used to produce pools of scientific literature of questionable value. We focus on HEp-2 [HeLa] and Intestine 407 [HeLa], two false cell lines that are widely used in the scientific literature but were shown to be cross-contaminated in 1967. These two cell lines have been used in 8497 and 1397 published articles and extensively described as laryngeal cancer and normal intestine, respectively, rather than their true identity: the cervical cancer cell line HeLa. Discussed are tools, approaches, and resources that can address this issue—both retrospectively and prospectively.

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Widespread distribution of a 210,000 mol wt microtubule-associated protein in cells and tissues of primates.

The Journal of Cell Biology ◽

10.1083/jcb.87.3.802 ◽

1980 ◽

Vol 87 (3) ◽

pp. 802-808 ◽

Cited By ~ 50

Author(s):

J C Bulinski ◽

G G Borisy

Keyword(s):

Human Cell Line ◽

Immunofluorescent Staining ◽

Reactive Material ◽

Widespread Distribution ◽

Cell Line Hela ◽

Indirect Immunofluorescence Technique ◽

Related Proteins ◽

Indirect Immunofluorescent ◽

Line Hela ◽

In Cells

Antisera prepared against a 210,000 mol wt microtubule-associated protein (210k MAP) isolated from the human cell line, HeLa, were used to survey a variety of cells and tissues for the presence of immunologically related proteins. The antisera were employed to test extracts of the cells and tissues, using a sensitive indirect immunofluorescence technique applied to polyacrylamide gels. Cross-reactive material of 210,000 mol wt was found in 10 kinds of cells and tissues derived from humans and four lines of cells from monkeys. Indirect immunofluorescent staining was also carried out on fixed cells and showed that the cross-reactive material was localized to interphase and mitotic microtubules as assayed in nine human and seven monkey cell lines. No protein that cross-reacted with 210k MAP antisera was detected in cells and tissues derived from two rodents, an ungulate, a marsupial, or a chicken. Therefore, the 210k MAP isolated from HeLa cells is present in a wide variety of cells and tissues of humans and other primates but is antigenically distinct from MAPs present in lower organisms.

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Evaluating the cytotoxicity of ionic liquids using human cell line HeLa

Human & Experimental Toxicology ◽

10.1191/0960327104ht480oa ◽

2004 ◽

Vol 23 (11) ◽

pp. 513-517 ◽

Cited By ~ 171

Author(s):

P Stepnowski ◽

A C Skladanowski ◽

A Ludwiczak ◽

E Laczyńska

Keyword(s):

Ionic Liquids ◽

Cell Line ◽

Human Tumor ◽

Tumor Cell Line ◽

Human Cell Line ◽

Imidazolium Ionic Liquids ◽

Cell Line Hela ◽

Order Of Magnitude ◽

Line Hela

This paper presents cytotoxicity data of selected imidazolium ionic liquids evaluated in vitro on the human tumor cell line HeLa. It was found that for 1-n-butyl-3-methylimidazolium entities the toxicity depends strongly on the associated anion; EC50 values are lowest for tetrafluoroborate. No direct dependence of the reduced effect concentration was found on elongating the short, methyl chain to ethyl or n-hexyl. Only for the ionic liquid with an n-decyl chain, the longest one studied, did higher hydrophobicity result in a EC50 one order of magnitude lower than that obtained with the n-butyl entity. The effect concentrations of imidazolium ionic liquids in the HeLa system used are lower than the values obtained for conventional organic solvents such as dichloromethane, toluene or xylene.

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Cytotoxicity of ionic liquids and precursor compounds towards human cell line HeLa

Green Chemistry ◽

10.1039/b704503d ◽

2007 ◽

Vol 9 (11) ◽

pp. 1191 ◽

Cited By ~ 131

Author(s):

Xuefeng Wang ◽

C. André Ohlin ◽

Qinghua Lu ◽

Zhaofu Fei ◽

Jun Hu ◽

...

Keyword(s):

Ionic Liquids ◽

Cell Line ◽

Human Cell ◽

Human Cell Line ◽

Cell Line Hela ◽

Line Hela

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Henrietta Lacks, HeLa Cells, and Cell Culture Contamination

Archives of Pathology & Laboratory Medicine ◽

10.5858/133.9.1463 ◽

2009 ◽

Vol 133 (9) ◽

pp. 1463-1467 ◽

Cited By ~ 4

Author(s):

Brendan P. Lucey ◽

Walter A. Nelson-Rees ◽

Grover M. Hutchins

Keyword(s):

Breast Cancer ◽

Cell Culture ◽

Cell Line ◽

Hela Cells ◽

Human Cell Line ◽

Hela Cell Line ◽

Cell Line Hela ◽

The World ◽

Cell Culture Contamination ◽

Line Hela

Abstract Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line.

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