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

Cell cycle Series of events and stages that result in cell division

The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm and other components into two daughter cells in a process called cell division.

Mitosis The division of a cell nucleus in which the genome is copied and separated into two identical halves

In cell biology, 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 often 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 mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other.

Microtubule 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 grow as long as 50 micrometres and are highly dynamic. The outer diameter of a microtubule is between 23 and 27 nm while the inner diameter is 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.

Cell division The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.

Cell division is the process by which a parent cell divides into two or more daughter cells. Cell division usually occurs as part of a larger cell cycle. In eukaryotes, there are two distinct types of cell division; a vegetative division, whereby each daughter cell is genetically identical to the parent cell (mitosis), and a reproductive cell division, whereby the number of chromosomes in the daughter cells is reduced by half to produce haploid gametes (meiosis). In cell biology, mitosis (/maɪˈtoʊsɪs/) 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 often 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 mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical daughter cells. Meiosis results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. 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.

Centrosome

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.

Cytokinesis

Cytokinesis is the part of the cell division process 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.

Cleavage furrow

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.

Telophase

Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.

Nondisjunction

Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division. 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 developmental biology, cleavage is the division of cells in the early embryo. The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex. 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.

Micronucleus

Micronucleus is the name given to the 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. Micronuclei form during anaphase from lagging acentric chromosome or chromatid fragments caused by incorrectly repaired or unrepaired DNA breaks or by nondisjunction of chromosomes. This incorrect segregation of chromosomes may result from hypomethylation of repeat sequences present in pericentromeric DNA, irregularities in kinetochore proteins or their assembly, dysfunctional spindle apparatus, or flawed anaphase checkpoint genes. Many micronucleus assays have been developed to test for the presence of these structures and determine their frequency in cells exposed to certain chemicals or subjected to stressful conditions.

Aurora A kinase

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

Phycoplast

The phycoplast is a microtubule structure observed during cytokinesis in members of the Chlorophyceae, the largest class of green algae.

Aurora B kinase

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

INCENP

Inner centromere protein is a protein that in humans is encoded by the INCENP gene.

TPX2

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.

Demecolcine

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.

Chromatin bridge

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.

Multipolar spindles

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.

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.
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