Caco-2 (from ''Cancer coli'', "colon cancer") is an

immortalized cell line An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...

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 application of Caco-2 cells in research was pioneered in the late 1980s by Ismael Hidalgo, working in the laboratory of Ron Borchardt at the University of Kansas, and Tom Raub, who was at the

Upjohn Company The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...

at the time. Following stints at

SmithKline Beecham GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

and Rhone-Poulenc Rorer, Hidalgo went on to co-found a company, in 1996, where he currently serves as Senior Vice President of Scientific Affairs.

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 digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before bein ...

)

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, mesoderm ...

, 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 (biology), morphology or physical form and structure, its Developmental biology, developmental proc ...

, 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 ...

. Polarized caco-2 cells express tight junctions,

microvilli Microvilli (singular: 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, ...

, and a number of

enzymes Enzymes () are proteins that act as biological catalysts 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 products. ...

and transporters that are characteristic of such enterocytes:

peptidase A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

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. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...

carboxylic acids In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

, etc.

Research applications

When looking at Caco-2 cell cultures microscopically, it is evident even by visual inspection that the cells are heterogeneous. This could probably be due to the fact that the epithelial lining of the large and small intestine typically comprises a heterogenous mixture of enterocytes, enteroendocrine cells, goblet cells, transit amplifying cells, paneth cells and intestinal stem cells. Over the years, the characteristics of the cells used in different laboratories around the world have diverged significantly, which makes it difficult to compare results across labs. Despite such heterogeneity, Caco-2 cells have found applications 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 naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...

transport. Caco-2 cells are most commonly used not as individual cells, but as a confluent

monolayer A monolayer is a single, closely packed layer of atoms, molecules, or cells. In some cases it is referred to as a self-assembled monolayer. Monolayers of layered crystals like graphene and molybdenum disulfide are generally called 2D materials. C ...

on a cell culture insert filter (e.g., Transwell). When cultured in this format, the cells differentiate to 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 is widely used across the pharmaceutical industry as an in vitro model of the human small intestinal mucosa to predict the absorption of orally administered drugs with different kits such as the CacoReady. The correlation between the in vitro apparent permeability (P¬app) across Caco-2 monolayers and the in vivo fraction absorbed (fa) is well established.Transwell diagram

References

External links

Cellosaurus entry for Caco-2
Human cell lines Colorectal cancer

History

Characteristics

Research applications

See also

References

Further reading

External links