Binucleated cells

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Binucleated cells
Binucleated cell overlay.tiff
A binucleated cell has two nuclei. The cell above was stained with DAPI to highlight the nuclei and treated with antibodies against tubulin to highlight the microtubules to show the binucleation.
Specialty Pathology


Binucleated cells are cells that contain two nuclei. This type of cell is most commonly found in cancer cells and may arise from a variety of causes. Binucleation can be easily visualized through staining and microscopy. In general, binucleation has negative effects on cell viability and subsequent mitosis.

Contents

They also occur physiologically in hepatocytes, chondrocytes and in fungi (dikaryon).

Causes

Cartoon of cleavage furrow formation and resolution. (A) depicts a normal cleavage furrow resolution. (B) depicts a cleavage furrow regression leading to a binucleated cell Cleavage Furrow Regression.svg
Cartoon of cleavage furrow formation and resolution. (A) depicts a normal cleavage furrow resolution. (B) depicts a cleavage furrow regression leading to a binucleated cell

Medical relevance

Detection

Binucleated cells can be observed using microscopy. Cells must first be fixed to arrest them wherever they are in the cell cycle and to keep their structures from degrading. Their nuclei and tubulin must next be made visible so that binucleation can be identified. DAPI is a dye that binds to DNA and fluoresces blue. For this reason, it is particularly useful at labeling nuclei. Antibody probes can be used to label tubulin fluorescently. The immunofluorescence may then be observed with microscopy. Binucleated cells are most easily identified by viewing tubulin, which surrounds the two nuclei in the cell. Binucleated cells may be mistaken for two cells in close proximity when viewing only nuclei.

The binucleated cell above is an oral squamous cell carcinoma, cell line UPCI-SCC-103. A: The cancer cell treated with antibodies against tubulin. B: The same cancer cell stained with DAPI, highlighting the nuclei. C: Both photos superimposed. Binucleated cell.jpg
The binucleated cell above is an oral squamous cell carcinoma, cell line UPCI-SCC-103. A: The cancer cell treated with antibodies against tubulin. B: The same cancer cell stained with DAPI, highlighting the nuclei. C: Both photos superimposed.

Cancer

Binucleation occurs at a much higher rate in cancer cells. [1] Other identifying features of cancer cells include multipolar spindles, micronuclei, and chromatin bridge. However, the increased rate of binucleation is usually not high enough to make it a conclusive diagnostic tool.

Effects

The fate of binucleated cells depends largely on the type of cell they originated from. [1] A large percentage of binucleated cells arising from normal cells remain in interphase and never enter mitosis again. [1] Cells that contain many mutations before they become binucleate are much more likely to proceed through subsequent rounds of mitosis. [1] One study found that more than 50% of binucleated cells never entered mitosis again while greater than 95% of cancer cells were able to proceed through mitosis. [1] Subsequent rounds of mitosis in binucleated cells have much higher rates of errors in chromosomal disjunction making it much more likely for cells to accumulate mutations. [1]

Related Research Articles

<span class="mw-page-title-main">Mitosis</span> Process in which chromosomes are replicated and separated into two new identical nuclei

Mitosis is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis is an equational division which gives rise to genetically identical cells in which the total number of chromosomes is maintained. Mitosis is preceded by the S phase of interphase and is followed by telophase and cytokinesis, which divide the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic phase of a cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Cell division</span> Process by which living cells divide

Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. Mitosis is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is followed by telophase and cytokinesis; which divides the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis all together define the M phase of an animal cell cycle—the division of the mother cell into two genetically identical daughter cells. To ensure proper progression through the cell cycle, DNA damage is detected and repaired at various checkpoints throughout the cycle. These checkpoints can halt progression through the cell cycle by inhibiting certain cyclin-CDK complexes. Meiosis undergoes two divisions resulting in four haploid daughter cells. Homologous chromosomes are separated in the first division of meiosis, such that each daughter cell has one copy of each chromosome. These chromosomes have already been replicated and have two sister chromatids which are then separated during the second division of meiosis. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

<span class="mw-page-title-main">Cytokinesis</span> Part of the cell division process

Cytokinesis is the part of the cell division process and part of mitosis during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.

<span class="mw-page-title-main">Cleavage furrow</span> Plasma membrane invagination at the cell division site

In cell biology, the cleavage furrow is the indentation of the cell's surface that begins the progression of cleavage, by which animal and some algal cells undergo cytokinesis, the final splitting of the membrane, in the process of cell division. The same proteins responsible for muscle contraction, actin and myosin, begin the process of forming the cleavage furrow, creating an actomyosin ring. Other cytoskeletal proteins and actin binding proteins are involved in the procedure.

<span class="mw-page-title-main">Nondisjunction</span> Failure to separate properly during cell division

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division (mitosis/meiosis). There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis. Nondisjunction results in daughter cells with abnormal chromosome numbers (aneuploidy).

In embryology, cleavage is the division of cells in the early development of the embryo, following fertilization. The zygotes of many species undergo rapid cell cycles with no significant overall growth, producing a cluster of cells the same size as the original zygote. The different cells derived from cleavage are called blastomeres and form a compact mass called the morula. Cleavage ends with the formation of the blastula, or of the blastocyst in mammals.

<span class="mw-page-title-main">Micronucleus</span> Small nucleus in the cells of some organisms

A micronucleus is a small nucleus that forms whenever a chromosome or a fragment of a chromosome is not incorporated into one of the daughter nuclei during cell division. It usually is a sign of genotoxic events and chromosomal instability. Micronuclei are commonly seen in cancerous cells and may indicate genomic damage events that can increase the risk of developmental or degenerative diseases.

<span class="mw-page-title-main">Aurora kinase A</span> Protein-coding gene in the species Homo sapiens

Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the AURKA gene.

<span class="mw-page-title-main">Phycoplast</span>

The phycoplast is a microtubule structure observed during cytokinesis in members of the Chlorophytina, the largest and most well known subphylum of chlorophyte green algae.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere and in cytokinesis.

<span class="mw-page-title-main">TPX2</span> Protein-coding gene in the species Homo sapiens

Targeting protein for Xklp2 is a protein that in humans is encoded by the TPX2 gene. It is one of the many spindle assembly factors that play a key role in inducing microtubule assembly and growth during M phase.

<span class="mw-page-title-main">PCNT</span> Protein-coding gene in the species Homo sapiens

Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the PCNT gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) to ensure proper centrosome and mitotic spindle formation, and thus, uninterrupted cell cycle progression. This gene is implicated in many diseases and disorders, including congenital disorders such as microcephalic osteodysplastic primordial dwarfism type II (MOPDII) and Seckel syndrome.

<span class="mw-page-title-main">Demecolcine</span> Chemical compound

Demecolcine is a drug used in chemotherapy. It is closely related to the natural alkaloid colchicine with the replacement of the acetyl group on the amino moiety with methyl, but it is less toxic. It depolymerises microtubules and limits microtubule formation, thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.

<span class="mw-page-title-main">Mitotic catastrophe</span> Mechanism of cell death

Mitotic catastrophe has been defined as either a cellular mechanism to prevent potentially cancerous cells from proliferating or as a mode of cellular death that occurs following improper cell cycle progression or entrance. Mitotic catastrophe can be induced by prolonged activation of the spindle assembly checkpoint, errors in mitosis, or DNA damage and operates to prevent genomic instability. It is a mechanism that is being researched as a potential therapeutic target in cancers, and numerous approved therapeutics induce mitotic catastrophe.

Amitosis, also known as karyostenosis, direct cell division, or binary fission, is a mode of asexual cell division primarily observed in prokaryotes. This process is distinct from other cell division mechanisms such as mitosis and meiosis, mainly because it bypasses the complexities associated with the mitotic apparatus, such as spindle formation. Additionally, amitosis does not involve the condensation of chromatin into distinct chromosomes before the cell divides, thereby simplifying the process of cellular replication.

<span class="mw-page-title-main">Chromatin bridge</span> Medical condition

Chromatin bridge is a mitotic occurrence that forms when telomeres of sister chromatids fuse together and fail to completely segregate into their respective daughter cells. Because this event is most prevalent during anaphase, the term anaphase bridge is often used as a substitute. After the formation of individual daughter cells, the DNA bridge connecting homologous chromosomes remains fixed. As the daughter cells exit mitosis and re-enter interphase, the chromatin bridge becomes known as an interphase bridge. These phenomena are usually visualized using the laboratory techniques of staining and fluorescence microscopy.

<span class="mw-page-title-main">Multipolar spindles</span>

Multipolar spindles are spindle formations characteristic of cancer cells. Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself. In a mitotic cell wherever two asters convene the formation of a spindle occurs.

The central spindle is a microtubule based structure, which forms in between segregating chromosomes during anaphase where the two sets of microtubules, emanating from opposite halves of the cell, overlap, and become arranged into antiparallel bundles by various microtubule associated proteins (MAPs) and motor proteins. The central spindle is widely regarded as a key regulating center for cytokinesis, recruiting proteins for successful cleavage furrow positioning and membrane abscission. For these important roles to be achieved successfully the central spindle has to be carefully regulated to control the size of the overlap region, the alignment of those overlaps and the overall length and symmetry of the structure. Without this regulation, signaling faults in cytokinesis can occur, resulting in unequal chromosome segregation or polyploid cells, greatly increasing the risk of cancer.

J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.

References

  1. 1 2 3 4 5 6 7 8 9 10 Shi, Qinghua; Randall W. King (13 October 2005). "Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines". Nature. 437 (7061): 1038–42. Bibcode:2005Natur.437.1038S. doi:10.1038/nature03958. PMID   16222248. S2CID   1093265.