CD133 antigen, also known as prominin-1, is a glycoprotein that in humans is encoded by the PROM1 gene.[5][6] 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.[7] While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.[8]
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CD133 is expressed in hematopoietic stem cells,[9] endothelial progenitor cells,[10] glioblastoma, neuronal and glial stem cells,[11] various pediatric brain tumors,[12] as well as adult kidney, mammary glands, trachea, salivary glands, uterus, placenta, digestive tract, testes, and some other cell types.[13][14][15]
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.[16] 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.[17][12][18][19] However, subsequent studies have indicated the difficulty in isolating pure CSC populations.[20] CD133+ melanoma cells are considered a subpopulation of CSC and play a critical role in recurrence.[21] 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.[22] 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.[23]
Corbeil D, Fargeas CA, Huttner WB (July 2001). "Rat prominin, like its mouse and human orthologues, is a pentaspan membrane glycoprotein". Biochemical and Biophysical Research Communications. 285 (4): 939–44. doi:10.1006/bbrc.2001.5271. PMID 11467842. Corbeil D, Karbanová J, Fargeas CA, Jászai J (2012-11-05). "Prominin-1 (CD133): Molecular and Cellular Features Across Species". Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology. Advances in Experimental Medicine and Biology. Vol. 777. pp. 3–24. doi:10.1007/978-1-4614-5894-4_1. ISBN 9781461458937. PMID 23161072. Horn PA, Tesch H, Staib P, Kube D, Diehl V, Voliotis D (February 1999). "Expression of AC133, a novel hematopoietic precursor antigen, on acute myeloid leukemia cells". Blood. 93 (4): 1435–7. doi:10.1182/blood.V93.4.1435. PMID 10075457. Sanai N, Alvarez-Buylla A, Berger MS (August 2005). "Neural stem cells and the origin of gliomas". The New England Journal of Medicine. 353 (8): 811–22. doi:10.1056/NEJMra043666. PMID 16120861. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (September 2003). "Identification of a cancer stem cell in human brain tumors". Cancer Research. 63 (18): 5821–8. PMID 14522905. Dowland SN, Madawala RJ, Poon CE, Lindsay LA, Murphy CR (June 2017). "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. doi:10.1071/RD15432. PMID 27166505. Kim YS, Kaidina AM, Chiang JH, Yarygin KN, Lupatov AY (2017). "Cancer stem cell molecular markers verified in vivo". Biochem. Moscow Suppl. Ser. B. 11 (1): 43–54. doi:10.1134/S1990750817010036. S2CID 90912166. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (October 2004). "Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma" (PDF). Cancer Research. 64 (19): 7011–21. doi:10.1158/0008-5472.CAN-04-1364. hdl:2434/585643. PMID 15466194. S2CID 14693017. 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 (February 2008). "CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells". International Journal of Cancer. 122 (4): 761–8. doi:10.1002/ijc.23130. PMID 17955491. S2CID 25435240. 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 (March 2007). "Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential". European Journal of Cancer. 43 (5): 935–46. doi:10.1016/j.ejca.2007.01.017. hdl:2434/28996. PMID 17320377. Miyabayashi T, Kagamu H, Koshio J, Ichikawa K, Baba J, Watanabe S, Tanaka H, Tanaka J, Yoshizawa H, Nakata K, Narita I (November 2011). "Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor". Cancer Immunology, Immunotherapy. 60 (11): 1597–608. doi:10.1007/s00262-011-1063-x. PMC 11029006. PMID 21691723. S2CID 25329727. Koshio J, Kagamu H, Nozaki K, Saida Y, Tanaka T, Shoji S, Igarashi N, Miura S, Okajima M, Watanabe S, Yoshizawa H, Narita I (October 2013). "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. doi:10.1007/s00262-013-1467-x. PMC 11028571. PMID 23974721. S2CID 25347678.
- Shimizu K, Itoh T, Shimizu M, Ku Y, Hori Y (November 2009). "CD133 expression pattern distinguishes intraductal papillary mucinous neoplasms from ductal adenocarcinomas of the pancreas" (PDF). Pancreas. 38 (8): e207-14. doi:10.1097/MPA.0b013e3181bb5037. PMID 19786935. S2CID 25675719. Archived from the original (PDF) on 2018-11-01. Retrieved 2018-10-31.
- 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 (September 2009). "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. Bibcode:2009PNAS..10616281B. doi:10.1073/pnas.0905653106. PMC 2741477. PMID 19805294.
- Salnikov AV, Gladkich J, Moldenhauer G, Volm M, Mattern J, Herr I (February 2010). "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. doi:10.1002/ijc.24822. PMID 19676044. S2CID 23335006.
- Nishide K, Nakatani Y, Kiyonari H, Kondo T (August 2009). Lowenstein PR (ed.). "Glioblastoma formation from cell population depleted of Prominin1-expressing cells". PLOS ONE. 4 (8): e6869. Bibcode:2009PLoSO...4.6869N. doi:10.1371/journal.pone.0006869. PMC 2729925. PMID 19718438.
- Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH, Park JH (2009). "Isolation and characterization of spheroid cells from human malignant melanoma cell line WM-266-4". Tumour Biology. 30 (5–6): 300–9. doi:10.1159/000261073. PMID 19940551. S2CID 40841423.
- Sun Y, Kong W, Falk A, Hu J, Zhou L, Pollard S, Smith A (2009). Chédotal A (ed.). "CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent". PLOS ONE. 4 (5): e5498. Bibcode:2009PLoSO...4.5498S. doi:10.1371/journal.pone.0005498. PMC 2676510. PMID 19430532.
- Wu X, Spitz MR, Lee JJ, Lippman SM, Ye Y, Yang H, Khuri FR, Kim E, Gu J, Lotan R, Hong WK (July 2009). "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. doi:10.1158/1940-6207.CAPR-09-0025. PMC 2964280. PMID 19584075.
- Yao J, Zhang T, Ren J, Yu M, Wu G (October 2009). "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. doi:10.3892/or_00000500. PMID 19724856.
- Yasuda H, Tanaka K, Saigusa S, Toiyama Y, Koike Y, Okugawa Y, Yokoe T, Kawamoto A, Inoue Y, Miki C, Kusunoki M (October 2009). "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. doi:10.3892/or_00000491. PMID 19724847.
- Yoshikawa S, Zen Y, Fujii T, Sato Y, Ohta T, Aoyagi Y, Nakanuma Y (October 2009). "Characterization of CD133+ parenchymal cells in the liver: histology and culture". World Journal of Gastroenterology. 15 (39): 4896–906. doi:10.3748/wjg.15.4896. PMC 2764966. PMID 19842219.
- Ferrandina G, Martinelli E, Petrillo M, Prisco MG, Zannoni G, Sioletic S, Scambia G (July 2009). "CD133 antigen expression in ovarian cancer". BMC Cancer. 9: 221. doi:10.1186/1471-2407-9-221. PMC 3224735. PMID 19583859.
- Wang Q, Chen ZG, Du CZ, Wang HW, Yan L, Gu J (September 2009). "Cancer stem cell marker CD133+ tumour cells and clinical outcome in rectal cancer". Histopathology. 55 (3): 284–93. doi:10.1111/j.1365-2559.2009.03378.x. PMID 19723143. S2CID 12088193.
- Friedman S, Lu M, Schultz A, Thomas D, Lin RY (2009). Breant B (ed.). "CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin". PLOS ONE. 4 (4): e5395. Bibcode:2009PLoSO...4.5395F. doi:10.1371/journal.pone.0005395. PMC 2671400. PMID 19404394.
- Cheng JX, Liu BL, Zhang X (August 2009). "How powerful is CD133 as a cancer stem cell marker in brain tumors?". Cancer Treatment Reviews. 35 (5): 403–8. doi:10.1016/j.ctrv.2009.03.002. PMID 19369008.
- Horst D, Kriegl L, Engel J, Kirchner T, Jung A (October 2009). "Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer". Cancer Investigation. 27 (8): 844–50. doi:10.1080/07357900902744502. PMID 19626493. S2CID 35888000.
- Yeh CT, Kuo CJ, Lai MW, Chen TC, Lin CY, Yeh TS, Lee WC (September 2009). "CD133-positive hepatocellular carcinoma in an area endemic for hepatitis B virus infection". BMC Cancer. 9: 324. doi:10.1186/1471-2407-9-324. PMC 2753636. PMID 19744348.
- Li CY, Li BX, Liang Y, Peng RQ, Ding Y, Xu DZ, Zhang X, Pan ZZ, Wan DS, Zeng YX, Zhu XF, Zhang XS (July 2009). "Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB". Journal of Translational Medicine. 7: 56. doi:10.1186/1479-5876-7-56. PMC 2715381. PMID 19583834.
- Hibi K, Sakata M, Sakuraba K, Shirahata A, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G, Nemoto H, Sanada Y (2009). "CD133 gene overexpression is frequently observed in early colorectal carcinoma". Hepato-Gastroenterology. 56 (93): 995–7. PMID 19760928.
- Pras E, Abu A, Rotenstreich Y, Avni I, Reish O, Morad Y, Reznik-Wolf H, Pras E (August 2009). "Cone-rod dystrophy and a frameshift mutation in the PROM1 gene". Molecular Vision. 15: 1709–16. PMC 2732717. PMID 19718270.
- 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 (July 2009). "Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors". Clinical Cancer Research. 15 (13): 4299–311. doi:10.1158/1078-0432.CCR-08-1883. PMID 19509143.