Caco-2 (from ''Cancer coli'', "colon cancer") is an
immortalized cell line of human
colorectal adenocarcinoma cells. It is primarily used as a model of the
intestinal epithelial barrier.
In culture, Caco-2 cells spontaneously differentiate into a heterogeneous mixture of
intestinal epithelial cells.
It was developed in 1977 by Jorgen Fogh at the
Sloan-Kettering Institute for Cancer Research.
History
The line was developed in 1977 by Jorgen Fogh at the
Sloan-Kettering Institute for Cancer Research.
The research application of Caco-2 cells was developed during the 1980s by Alain Zweibaum group at INSERM, France as well as Ismael Hidalgo, at the Borchardt laboratory, University of Kansas and Tom Rauband at the
Upjohn Company. The first publication of the discovery of the spontaneous enterocyte like differentiation was published by Alain Zweibaum group in 1983.
Characteristics
Although derived from a colon (
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the Digestion, digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces befor ...
)
carcinoma
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 ...
, when cultured under specific conditions the cells become differentiated and polarized such that their
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
, morphologically and functionally, resembles the
enterocytes
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase i ...
lining the
small intestine
The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
.
microvilli
Microvilli (: microvillus) are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, cellula ...
, and a number of enzymes
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
and transporters that are characteristic of such enterocytes: peptidase
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...
s, esterases, P-glycoprotein
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
, uptake transporters for amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
, bile acids
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
, carboxylic acids
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...
, etc.
Research applications
Microscopically, Caco-2 cell cultures show obvious heterogeneity likely reflecting the complex mixture of cells found in the epithelial lining of the large and small intestine i.e. enterocytes, enteroendocrine cells, goblet cells, transit amplifying cells, paneth cells and intestinal stem cells. Over time, the characteristics of the cells used in different laboratories have diverged, introducing inter-laboratory variation. Despite such heterogeneity, Caco-2 cells are used in cell invasion studies, viral transfection
Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: " transformation" is typically used to des ...
research, and lipid
Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
transport.monolayer
A monolayer is a single, closely packed layer of entities, commonly atoms or molecules.
Monolayers can also be made out of cells. ''Self-assembled monolayers'' form spontaneously on surfaces. Monolayers of layered crystals like graphene and molyb ...
on a cell culture insert filter (e.g., Transwell). In this format, Caco-2 cells form a polarized epithelial cell monolayer that provides a physical and biochemical barrier to the passage of ions and small molecules.[ The Caco-2 monolayer can be used as an ''in vitro'' model of the human small intestinal mucosa to predict the absorption of orally administered drugs. Kits, such as the CacoReady, have been developed to simplify this procedure. A correlation between the ''in vitro'' apparent permeability across Caco-2 monolayers and the ''in vivo'' fraction absorbed has been reported.][Transwell diagram]
See also
*Cell culture
Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...
*Drug development
Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for regu ...
* Pre-clinical development
*PAMPA
The Pampas (; from Quechuan languages, Quechua 'plain'), also known as the Pampas Plain, are fertile South American low grasslands that cover more than and include the Argentina, Argentine Provinces of Argentina, provinces of Buenos Aires Pro ...
– a non cell-based permeability assay
References
Further reading
*
*
{{refend
External links
Cellosaurus entry for Caco-2
Human cell lines
Colorectal cancer