Phase contrast micrograph of confluent Caco-2 cells.

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.[1] In culture, Caco-2 cells spontaneously differentiate into a heterogeneous mixture of intestinal epithelial cells.[1] It was developed in 1977 by Jorgen Fogh at the Sloan-Kettering Institute for Cancer Research.[2]

History

The line was developed in 1977 by Jorgen Fogh at the Sloan-Kettering Institute for Cancer Research.[2] 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 spontenous enterocyte like differentiation was published by Alain Zweibaum group in 1983 (3).

Characteristics

Although derived from a colon (large intestine) carcinoma, when cultured under specific conditions the cells become differentiated and polarized such that their phenotype, morphologically and functionally, resembles the enterocytes lining the small intestine.[3][4] Polarized caco-2 cells express tight junctions, microvilli, and a number of enzymes and transporters that are characteristic of such enterocytes: peptidases, esterases, P-glycoprotein, uptake transporters for amino acids, bile acids, carboxylic acids, 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.[5] Over time, the characteristics of the cells used in different laboratories have diverged, introducing inter-laboratory variation.[6] Despite such heterogeneity, Caco-2 cells are used in cell invasion studies, viral transfection research, and lipid transport.[7]

Caco-2 cells may be used as a confluent monolayer 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.[4][8] 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.[9] A correlation between the in vitro apparent permeability across Caco-2 monolayers and the in vivo fraction absorbed has been reported.[10] Transwell diagram

See also

References

  1. 1 2 Lea, Tor (2015). "Caco-2 Cell Line". The Impact of Food Bioactives on Health: 103–111. doi:10.1007/978-3-319-16104-4_10. ISBN 978-3-319-15791-7. PMID 29787057.
  2. 1 2 Fogh, Jørgen; Fogh, Jens M.; Orfeo, Thomas (July 1977). "One Hundred and Twenty-Seven Cultured Human Tumor Cell Lines Producing Tumors in Nude Mice23". JNCI: Journal of the National Cancer Institute. 59 (1): 221–226. doi:10.1093/jnci/59.1.221. PMID 327080.
  3. ↑ Pinto M (1983). "Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture". Biol Cell. 47: 323–30.
  4. 1 2 Hidalgo IJ, Raub TJ, Borchardt RT (March 1989). "Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability". Gastroenterology. 96 (3): 736–49. doi:10.1016/0016-5085(89)90897-4. PMID 2914637.
  5. ↑ Dey, Isha; Bradbury, Neil A. (2018-01-01), Levitane, Irena; Delpire, Eric; Rasgado-Flores, Hector (eds.), "Chapter Ten - Physiology of the Gut: Experimental Models for Investigating Intestinal Fluid and Electrolyte Transport", Current Topics in Membranes, Cell Volume Regulation, Academic Press, 81: 337–381, doi:10.1016/bs.ctm.2018.08.003, PMID 30243437, retrieved 2022-04-01
  6. ↑ Sambuy Y, De Angelis I, Ranaldi G, Scarino ML, Stammati A, Zucco F (January 2005). "The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics". Cell Biology and Toxicology. 21 (1): 1–26. doi:10.1007/s10565-005-0085-6. PMID 15868485. S2CID 125735.
  7. ↑ Nauli AM, Whittimore JD (August 2015). "Using Caco-2 Cells to Study Lipid Transport by the Intestine". Journal of Visualized Experiments (102): e53086. doi:10.3791/53086. PMC 4692536. PMID 26325673.
  8. ↑ Artursson P (June 1990). "Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells". Journal of Pharmaceutical Sciences. 79 (6): 476–82. doi:10.1002/jps.2600790604. PMID 1975619.
  9. ↑ Vázquez-Sánchez MÁ. "CacoReady". Readycell. Readycell. Archived from the original on 2022-01-13. Retrieved 19 July 2018.
  10. ↑ Artursson P, Karlsson J (March 1991). "Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells". Biochemical and Biophysical Research Communications. 175 (3): 880–5. doi:10.1016/0006-291X(91)91647-U. PMID 1673839.

Further reading

  • Artursson P, Palm K, Luthman K (March 2001). "Caco-2 monolayers in experimental and theoretical predictions of drug transport". Advanced Drug Delivery Reviews. 46 (1–3): 27–43. doi:10.1016/S0169-409X(00)00128-9. PMID 11259831.
  • Shah P, Jogani V, Bagchi T, Misra A (2006). "Role of Caco-2 cell monolayers in prediction of intestinal drug absorption". Biotechnology Progress. 22 (1): 186–98. doi:10.1021/bp050208u. PMID 16454510. S2CID 37725450.
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