CD133 explained

CD133 antigen, also known as prominin-1, is a glycoprotein that in humans is encoded by the PROM1 gene.^{[1] [2]} It is a member of pentaspan transmembrane glycoproteins, which specifically localize to cellular protrusions. When embedded in the cell membrane, the membrane topology of prominin-1 is such that the N-terminus extends into the extracellular space 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.^[3] While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.^[4]

Tissue distribution

CD133 is expressed in hematopoietic stem cells,^[5] endothelial progenitor cells,^[6] glioblastoma, neuronal and glial stem cells,^[7] various pediatric brain tumors,^[8] as well as adult kidney, mammary glands, trachea, salivary glands, uterus, placenta, digestive tract, testes, and some other cell types.^{[9] [10] [11]}

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 and carcinomas.^[12] 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.^{[13] [14] [15]} However, subsequent studies have indicated the difficulty in isolating pure CSC populations.^[16] CD133⁺ melanoma cells are considered a subpopulation of CSC and play a critical role in recurrence.^[17] Moreover, CD133⁺ melanoma cells are immunogenic 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.^[18] In addition, it has also been shown that CD133⁺ melanoma cells preferentially express the RNA helicase DDX3X. As DDX3X also is an immunogenic protein, the same anti-melanoma vaccination strategy can be employed to give therapeutic antitumor immunity in mice.^[19]

See also

• Stargardt disease

Further reading

• Shimizu K, Itoh T, Shimizu M, Ku Y, Hori Y . CD133 expression pattern distinguishes intraductal papillary mucinous neoplasms from ductal adenocarcinomas of the pancreas . Pancreas . 38 . 8 . e207-14 . November 2009 . 19786935 . 10.1097/MPA.0b013e3181bb5037 . 25675719 . 2018-10-31 . 2018-11-01 . https://web.archive.org/web/20181101015539/http://www.lib.kobe-u.ac.jp/repository/90001574.pdf . dead .
• Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, Pratesi G, Fabbri A, Andriani F, Tinelli S, Roz E, Caserini R, Lo Vullo S, Camerini T, Mariani L, Delia D, Calabrò E, Pastorino U, Sozzi G . Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment . Proceedings of the National Academy of Sciences of the United States of America . 106 . 38 . 16281–6 . September 2009 . 19805294 . 2741477 . 10.1073/pnas.0905653106 . 2009PNAS..10616281B . free .
• Salnikov AV, Gladkich J, Moldenhauer G, Volm M, Mattern J, Herr I . CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients . International Journal of Cancer . 126 . 4 . 950–8 . February 2010 . 19676044 . 10.1002/ijc.24822 . 23335006 . free .
• Nishide K, Nakatani Y, Kiyonari H, Kondo T . Glioblastoma formation from cell population depleted of Prominin1-expressing cells . PLOS ONE . 4 . 8 . e6869 . August 2009 . 19718438 . 2729925 . 10.1371/journal.pone.0006869 . Lowenstein . Pedro R. . 2009PLoSO...4.6869N . free .
• Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH, Park JH . Isolation and characterization of spheroid cells from human malignant melanoma cell line WM-266-4 . Tumour Biology . 30 . 5–6 . 300–9 . 2009 . 19940551 . 10.1159/000261073 . 40841423 .
• Sun Y, Kong W, Falk A, Hu J, Zhou L, Pollard S, Smith A . CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent . PLOS ONE . 4 . 5 . e5498 . 2009 . 19430532 . 2676510 . 10.1371/journal.pone.0005498 . Chédotal . Alain . 2009PLoSO...4.5498S . free .
• Wu X, Spitz MR, Lee JJ, Lippman SM, Ye Y, Yang H, Khuri FR, Kim E, Gu J, Lotan R, Hong WK . Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants . Cancer Prevention Research . 2 . 7 . 617–24 . July 2009 . 19584075 . 2964280 . 10.1158/1940-6207.CAPR-09-0025 .
• Yao J, Zhang T, Ren J, Yu M, Wu G . Effect of CD133/prominin-1 antisense oligodeoxynucleotide on in vitro growth characteristics of Huh-7 human hepatocarcinoma cells and U251 human glioma cells . Oncology Reports . 22 . 4 . 781–7 . October 2009 . 19724856 . 10.3892/or_00000500 . free .
• Yasuda H, Tanaka K, Saigusa S, Toiyama Y, Koike Y, Okugawa Y, Yokoe T, Kawamoto A, Inoue Y, Miki C, Kusunoki M . Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer . Oncology Reports . 22 . 4 . 709–17 . October 2009 . 19724847 . 10.3892/or_00000491 . free .
• Yoshikawa S, Zen Y, Fujii T, Sato Y, Ohta T, Aoyagi Y, Nakanuma Y . Characterization of CD133+ parenchymal cells in the liver: histology and culture . World Journal of Gastroenterology . 15 . 39 . 4896–906 . October 2009 . 19842219 . 2764966 . 10.3748/wjg.15.4896 . free .
• Ferrandina G, Martinelli E, Petrillo M, Prisco MG, Zannoni G, Sioletic S, Scambia G . CD133 antigen expression in ovarian cancer . BMC Cancer . 9 . 221 . July 2009 . 19583859 . 3224735 . 10.1186/1471-2407-9-221 . free .
• Wang Q, Chen ZG, Du CZ, Wang HW, Yan L, Gu J . Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer . Histopathology . 55 . 3 . 284–93 . September 2009 . 19723143 . 10.1111/j.1365-2559.2009.03378.x . 12088193 .
• Friedman S, Lu M, Schultz A, Thomas D, Lin RY . CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin . PLOS ONE . 4 . 4 . e5395 . 2009 . 19404394 . 2671400 . 10.1371/journal.pone.0005395 . Breant . Bernadette . 2009PLoSO...4.5395F . free .
• Cheng JX, Liu BL, Zhang X . How powerful is CD133 as a cancer stem cell marker in brain tumors? . Cancer Treatment Reviews . 35 . 5 . 403–8 . August 2009 . 19369008 . 10.1016/j.ctrv.2009.03.002 .
• Horst D, Kriegl L, Engel J, Kirchner T, Jung A . Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer . Cancer Investigation . 27 . 8 . 844–50 . October 2009 . 19626493 . 10.1080/07357900902744502 . 35888000 .
• Yeh CT, Kuo CJ, Lai MW, Chen TC, Lin CY, Yeh TS, Lee WC . CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection . BMC Cancer . 9 . 324 . September 2009 . 19744348 . 2753636 . 10.1186/1471-2407-9-324 . free .
• Li CY, Li BX, Liang Y, Peng RQ, Ding Y, Xu DZ, Zhang X, Pan ZZ, Wan DS, Zeng YX, Zhu XF, Zhang XS . Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB . Journal of Translational Medicine . 7 . 56 . July 2009 . 19583834 . 2715381 . 10.1186/1479-5876-7-56 . free .
• Hibi K, Sakata M, Sakuraba K, Shirahata A, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G, Nemoto H, Sanada Y . CD133 gene overexpression is frequently observed in early colorectal carcinoma . Hepato-Gastroenterology . 56 . 93 . 995–7 . 2009 . 19760928 .
• Pras E, Abu A, Rotenstreich Y, Avni I, Reish O, Morad Y, Reznik-Wolf H, Pras E . Cone-rod dystrophy and a frameshift mutation in the PROM1 gene . Molecular Vision . 15 . 1709–16 . August 2009 . 19718270 . 2732717 .
• Rutella S, Bonanno G, Procoli A, Mariotti A, Corallo M, Prisco MG, Eramo A, Napoletano C, Gallo D, Perillo A, Nuti M, Pierelli L, Testa U, Scambia G, Ferrandina G . Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors . Clinical Cancer Research . 15 . 13 . 4299–311 . July 2009 . 19509143 . 10.1158/1078-0432.CCR-08-1883 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview

Notes and References

1. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW . AC133, a novel marker for human hematopoietic stem and progenitor cells . Blood . 90 . 12 . 5002–12 . December 1997 . 10.1182/blood.V90.12.5002 . 9389720 . free .
2. Corbeil D, Fargeas CA, Huttner WB . Rat prominin, like its mouse and human orthologues, is a pentaspan membrane glycoprotein . Biochemical and Biophysical Research Communications . 285 . 4 . 939–44 . July 2001 . 11467842 . 10.1006/bbrc.2001.5271 .
3. Book: Corbeil D, Karbanová J, Fargeas CA, Jászai J . Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology . Prominin-1 (CD133): Molecular and Cellular Features Across Species . Advances in Experimental Medicine and Biology . 777 . 3–24 . 2012-11-05 . 23161072 . 10.1007/978-1-4614-5894-4_1 . 9781461458937 .
4. Irollo E, Pirozzi G . CD133: to be or not to be, is this the real question? . American Journal of Translational Research . 5 . 6 . 563–81 . September 2013 . 24093054 . 3786264 .
5. Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D . Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells . Blood . 93 . 4 . 1435–7 . February 1999 . 10.1182/blood.V93.4.1435 . 10075457 .
6. Corbeil D, Röper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB . The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions . The Journal of Biological Chemistry . 275 . 8 . 5512–20 . February 2000 . 10681530 . 10.1074/jbc.275.8.5512 . free .
7. Sanai N, Alvarez-Buylla A, Berger MS . Neural stem cells and the origin of gliomas . The New England Journal of Medicine . 353 . 8 . 811–22 . August 2005 . 16120861 . 10.1056/NEJMra043666 .
8. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB . Identification of a cancer stem cell in human brain tumors . Cancer Research . 63 . 18 . 5821–8 . September 2003 . 14522905 .
9. Mizrak D, Brittan M, Alison M . CD133: molecule of the moment . The Journal of Pathology . 214 . 1 . 3–9 . January 2008 . 18067118 . 10.1002/path.2283 . 44681326 .
10. Shmelkov SV, St Clair R, Lyden D, Rafii S . AC133/CD133/Prominin-1 . The International Journal of Biochemistry & Cell Biology . 37 . 4 . 715–9 . April 2005 . 15694831 . 10.1016/j.biocel.2004.08.010 .
11. Dowland SN, Madawala RJ, Poon CE, Lindsay LA, Murphy CR . Prominin-1 glycosylation changes throughout early pregnancy in uterine epithelial cells under the influence of maternal ovarian hormones . Reproduction, Fertility, and Development . 29 . 6 . 1194–1208 . June 2017 . 27166505 . 10.1071/RD15432 .
12. Kim YS, Kaidina AM, Chiang JH, Yarygin KN, Lupatov AY . Cancer stem cell molecular markers verified in vivo . Biochem. Moscow Suppl. Ser. B . 11 . 1 . 43–54 . 2017 . 10.1134/S1990750817010036 . 90912166 .
13. Lai IC, Shih PH, Yao CJ, Yeh CT, Wang-Peng J, Lui TN, Chuang SE, Hu TS, Lai TY, Lai GM . Elimination of cancer stem-like cells and potentiation of temozolomide sensitivity by Honokiol in glioblastoma multiforme cells . PLOS ONE . 10 . 3 . e0114830 . 2015 . 25763821 . 10.1371/journal.pone.0114830 . 4357432 . 2015PLoSO..1014830L . free .
14. Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI . Cancerous stem cells can arise from pediatric brain tumors . Proceedings of the National Academy of Sciences of the United States of America . 100 . 25 . 15178–83 . December 2003 . 14645703 . 299944 . 10.1073/pnas.2036535100 . 2003PNAS..10015178H . free .
15. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A . Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma . Cancer Research . 64 . 19 . 7011–21 . October 2004 . 15466194 . 10.1158/0008-5472.CAN-04-1364 . 2434/585643 . 14693017 . free .
16. Wang J, Sakariassen PØ, Tsinkalovsky O, Immervoll H, Bøe SO, Svendsen A, Prestegarden L, Røsland G, Thorsen F, Stuhr L, Molven A, Bjerkvig R, Enger PØ . CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells . International Journal of Cancer . 122 . 4 . 761–8 . February 2008 . 17955491 . 10.1002/ijc.23130 . 25435240 . free .
17. Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, Cavazzin C, Gritti A, Piccinini A, Porro D, Santinami M, Invernici G, Parati E, Alessandri G, La Porta CA . Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential . European Journal of Cancer . 43 . 5 . 935–46 . March 2007 . 17320377 . 10.1016/j.ejca.2007.01.017 . 2434/28996 . free .
18. Miyabayashi T, Kagamu H, Koshio J, Ichikawa K, Baba J, Watanabe S, Tanaka H, Tanaka J, Yoshizawa H, Nakata K, Narita I . Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor . Cancer Immunology, Immunotherapy . 60 . 11 . 1597–608 . November 2011 . 21691723 . 10.1007/s00262-011-1063-x . 25329727 . 11029006 .
19. Koshio J, Kagamu H, Nozaki K, Saida Y, Tanaka T, Shoji S, Igarashi N, Miura S, Okajima M, Watanabe S, Yoshizawa H, Narita I . DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells . Cancer Immunology, Immunotherapy . 62 . 10 . 1619–28 . October 2013 . 23974721 . 10.1007/s00262-013-1467-x . 25347678 . 11028571 .