CD133 antigen, also known as prominin-1, is a
glycoprotein that in humans is encoded by the ''PROM1''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. It is a member of pentaspan
transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
glycoproteins, which specifically localize to cellular protrusions. When embedded in the
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, the
membrane topology
Topology of a transmembrane protein refers to locations of N- and C-termini of membrane-spanning polypeptide chain with respect to the inner or outer sides of the biological membrane occupied by the protein.
Several databases provide experimenta ...
of prominin-1 is such that the
N-terminus extends into the
extracellular space
Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells.
The compos ...
and the
C-terminus resides in the intracellular compartment. The protein consists of five transmembrane segments, with the first and second segments and the third and fourth segments connected by intracellular loops while the second and third as well as fourth and fifth transmembrane segments are connected by extracellular loops. While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.
Tissue distribution
CD133 is expressed in
hematopoietic stem cells
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...
,
endothelial progenitor cell
Endothelial progenitor cell (or EPC) is a term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels. Outgrowth endothelial cells are an EPC subtype committed to endot ...
s,
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...
,
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
al and
glial stem cells, various pediatric brain tumors,
as well as adult kidney, mammary glands, trachea, salivary glands, uterus, placenta, digestive tract, testes, and some other cell types.
Clinical significance
Today CD133 is the most commonly used marker for isolation of
cancer stem cell (CSC) population from different tumors, mainly from various
gliomas
A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.
Signs and symptoms
...
and
carcinomas
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...
. Initial studies that showed ability of CD133-positive population to efficiently propagate tumor when injected into
immune-compromised mice firstly were performed on brain tumors.
However, subsequent studies have indicated the difficulty in isolating pure CSC populations. CD133
+ melanoma cells are considered a subpopulation of CSC and play a critical role in recurrence.
Moreover, CD133
+ melanoma cells are
immunogenic
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:
* Wanted immunogenicity typically relates to vaccines, where the injectio ...
and can be used as an antimelanoma vaccination. In mice the vaccination with CD133
+ melanoma cells mediated strong anti-tumor activity that resulted in the eradication of parental melanoma cells.
In addition, it has also been shown that CD133
+ melanoma cells preferentially express the RNA helicase
DDX3X
ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the ''DDX3X'' gene.
Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a numbe ...
. As DDX3X also is an immunogenic protein, the same anti-melanoma vaccination strategy can be employed to give therapeutic antitumor immunity in mice.
See also
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Stargardt disease
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview*
{{Clusters of differentiation
Molecular biology