Binucleated cells
Encyclopedia
Binucleated cells simply 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
.
. 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.
cells. Other identifying features of cancer
cells include multipolar spindles
, micronuclei, and anaphase bridges. However, the increased rate of binucleation is usually not high enough to make it a conclusive diagnostic tool.
and never enter mitosis
again. Cells that contain many mutations before they become binucleate are much more likely to proceed through subsequent rounds of mitosis
. 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
. 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.
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
. This type of cell is most commonly found in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells and may arise from a variety of causes. Binucleation can be easily visualized through staining and microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
. In general, binucleation has negative effects on cell viability and subsequent mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
.
Causes
- Cleavage furrowCleavage furrowIn cell biology, the cleavage furrow is the indentation that begins the process of cleavage, by which animal and some algal cells undergo cytokinesis. The same proteins responsible for muscle contraction, actin and myosin begin the process of forming the cleavage furrow. This can only happen in...
regression: Cells divide and almost complete division but then the cleavage furrowCleavage furrowIn cell biology, the cleavage furrow is the indentation that begins the process of cleavage, by which animal and some algal cells undergo cytokinesis. The same proteins responsible for muscle contraction, actin and myosin begin the process of forming the cleavage furrow. This can only happen in...
begins to regress and the cells merge. This is thought to be caused by nondisjunctionNondisjunctionNondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
in chromosomes but the mechanism by which it occurs is not well understood.
- Failed cytokinesisCytokinesisCytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...
: The cell can fail to form a cleavage furrowCleavage furrowIn cell biology, the cleavage furrow is the indentation that begins the process of cleavage, by which animal and some algal cells undergo cytokinesis. The same proteins responsible for muscle contraction, actin and myosin begin the process of forming the cleavage furrow. This can only happen in...
, leading to a both nuclei remaining in one cell. - Multipolar spindlesMultipolar spindlesMultipolar spindles are spindle formations characteristic of cancer cells. Spindle formation is mostly conducted by the aster of the centrosome which it forms around itself...
: Cells contain three or more centromeres, resulting in multiple poles. This leads to the cells pulling chromosomes in many directions that end in multiple nucleiCell nucleusIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
found in one cell. - Merging of newly formed cells: Two cells that have just finished cytokinesisCytokinesisCytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...
merge into one another. This process is not entirely understood.
Detection
Binucleated cells can be observed using microscopyMicroscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
. Cells must first be fixed
Fixation (histology)
In the fields of histology, pathology, and cell biology, fixation is a chemical process by which biological tissues are preserved from decay, thereby preventing autolysis or putrefaction...
to arrest them wherever they are in the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
and to keep their structures from degrading. Their nuclei
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
and tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
must next be made visible so that binucleation can be identified. DAPI
DAPI
DAPI or 4',6-diamidino-2-phenylindole is a fluorescent stain that binds strongly to A-T rich regions in DNA. It is used extensively in fluorescence microscopy...
is a dye that binds to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and fluoresces blue. For this reason, it is particularly useful at labeling nuclei. Antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
probes can be used to label tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
fluorescently. The immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
may then be observed with microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
. Binucleated cells are most easily identified by viewing tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
, which surrounds the two nuclei in the cell. Binucleated cells may be mistaken for two cells in close proximity when viewing only nuclei.
Cancer
Binucleation occurs at a much higher rate in cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells. Other identifying features of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells include multipolar spindles
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...
, micronuclei, and anaphase bridges. 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. A large percentage of binucleated cells arising from normal cells remain in interphaseInterphase
Interphase is the phase of the cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for cell division. In preparation for cell division, it increases its size and makes a copy of its DNA...
and never enter mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
again. Cells that contain many mutations before they become binucleate are much more likely to proceed through subsequent rounds of mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
. One study found that more than 50% of binucleated cells never entered mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
again while greater than 95% of cancer cells were able to proceed through mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
. Subsequent rounds of mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
in binucleated cells have much higher rates of errors in chromosomal disjunction making it much more likely for cells to accumulate mutations.